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.

[Detecting adverse drug events during the hospital stay]. / Detección de acontecimientos adversos producidos por medicamentos durante la estancia hospitalaria.

INTRODUCTION: The principal objective was to determine the incidence rate of adverse drug events (ADEs) in hospitalised patients and evaluate the event prevention percentage. METHODS: Multi-centre, prospective observational study lasting four months, performed in five hospitals providing different levels of care. We included all adult patients who were admitted to one of the selected centres for longer than 48 hours and who required pharmacological treatment. ADEs were identified by direct observation and the use of previously defined alarm signals. The Karch-Lasagna scale was used to determine the causality relationship, and the Schumock and Thornton questionnaire adapted by Otero was used to evaluate ADE preventability. Preventable drug-induced adverse events were classified according to the taxonomy that the Ruiz-Jarabo 2000 group defined, and coordinated by ISMP-Spain. RESULTS: We included 1,550 patients, 159 of whom experienced at least one ADE (10.3 %). The preventability percentage was 51.6 %, which represented 5.3 % of the total sample. The endocrine system (34.8 %) and the cardiovascular system (20.7 %) were the most affected by preventable ADEs. Antibiotics were responsible for 16.5 % of all ADEs. 9.3 % of all preventable ADEs were triggered by use of opiates. The vast majority of preventable ADEs (36.3 %) resulted from omitting a necessary medication. Only 4.4 % of preventable ADEs are considered to be serious. CONCLUSIONS: There is a high incidence rate of ADEs during patients' hospital stay (10.3 %), and half of them (51.6 %) could have been prevented. Implementation of an automatic alarm system and certain best practices for problem spots along the care circuit will help detect and avoid preventable ADEs.

Detección de acontecimientos adversos producidos por medicamentos durante la estancia hospitalaria / Detecting adverse drug events during the hospital stay

Introducción: El objetivo principal ha sido determinar la incidencia de acontecimientos adversos producidos por medicamentos (AAM) en pacientes hospitalizados y evaluar su porcentaje de prevención. Métodos: Estudio multicéntrico, prospectivo y observacional de 4 meses de duración, realizado en cinco hospitales de distinto nivel asistencial. Se incluyó a todos los pacientes adultos que ingresaron por más de 48 h en alguna de las unidades seleccionadas y requirieron tratamiento farmacológico. La identificación de los AAM se realizó mediante la observación directa y la utilización de unas señales de alerta, previamente definidas. Se utilizó el algoritmo de Karch-Lasagna, para determinar la relación de causalidad, y el cuestionario de Schumock y Thornton adaptado por Otero et al para evaluar la evitabilidad del AAM. Los AAM prevenibles se clasificaron siguiendo la taxonomía definida por el Grupo Ruiz-Jarabo 2000, coordinado por el ISMP-España. Resultados: Se incluyó a 1.550 pacientes, de los que 159 presentaron, al menos, un AAM (10,3 %). La tasa de evitabilidad fue del 51,6 %, lo que representa un 5,3 % de la muestra total. El sistema endocrino (34,8 %) y el cardiovascular (20,7 %) fueron los más afectados por los AAM prevenibles. Los antibióticos representaron el 16,5 % de todos los AAM. En cuanto a los AAM prevenibles, el 9,3 % de ellos se desencadenaron por la utilización de opiáceos. La gran mayoría de los AAM evitables fue consecuencia de la omisión de un medicamento necesario (36,3 %). Sólo un 4,4 % de los AAM evitables se consideró graves. Conclusiones: La incidencia de pacientes con AAM durante la estancia hospitalaria es alta (10,3 %), y la mitad de ellos (51,6 %) se podría haber prevenido. La implantación de un sistema automático de alertas y ciertas prácticas de mejoras en los puntos conflictivos del circuito sanitario ayudarían a la detección y la prevención de los AAM evitable (AU)

Introduction: The principal objective was to determine the incidence rate of adverse drug events (ADEs) in hospitalised patients and evaluate the event prevention percentage. Methods: Multi-centre, prospective observational study lasting four months, performed in five hospitals providing different levels of care. We included all adult patients who were admitted to one of the selected centres for longer than 48 hours and who required pharmacological treatment. ADEs were identifi ed by direct observation and the use of previously defi ned alarm signals. The Karch-Lasagna scale was used to determine the causality relationship, and the Schumock and Thornton questionnaire adapted by Otero was used to evaluate ADE preventability. Preventable drug-induced adverse events were classifi ed according to the taxonomy that the Ruiz-Jarabo 2000 group defi ned, and coordinated by ISMP-Spain. Results: We included 1,550 patients, 159 of whom experienced at least one ADE (10.3 %). The preventability percentage was 51.6 %, which represented 5.3 % of the total sample. The endocrine system (34.8 %) and the cardiovascular system (20.7 %) were the most affected by preventable ADEs. Antibiotics were responsible for 16.5 % of all ADEs. 9.3 % of all preventable ADEs were triggered by use of opiates. The vast majority of preventable ADEs (36.3 %) resulted from omitting a necessary medication. Only 4.4 % of preventable ADEs are considered to be serious. Conclusions: There is a high incidence rate of ADEs during patients’ hospital stay (10.3 %), and half of them (51.6 %) could have been prevented. Implementation of an automatic alarm system and certain best practices for problem spots along the care circuit will help detect and avoid preventable ADEs (AU)

[Evaluation of a pharmaceutical care program to improve adherence to antiretroviral therapy]. / Evaluación de un programa de atención farmacéutica dirigido a mejorar la adherencia al tratamiento antirretroviral.

OBJECTIVE: To establish the impact of a pharmaceutical care program on the improvement of adherence to antiretroviral therapy, and on patient immunologic and virologic outcome. MATERIALS AND METHODS: A multicenter, observational, prospective study in a HIV-infected patient cohort under treatment with antiretrovirals selected by random sampling in 19 Spanish hospitals. The study lasted 12 months, in which the program was applied through a baseline preprocedural visit and 4 quarterly visits. Adherence estimation was based on pill counting. An adherence > or = 90, or > or = 95% was considered adequate (in two time points). RESULTS: 541 patients were included, most of them were males (68.8%) between 20 and 78 years of age. Major risk groups included injecting drug users (43.4%) and heterosexuals (29.4%). Sixty percent had already received treatment for more than 3 years. Mean baseline viral load and CD4 count values were 32,866 copies/ml and 485 cells/mm3, respectively. Throughout the study a slight increase in the percentage of adherent patients was seen; however, statistical significance was not reached (64.3 and 79.2% of patients showed an adherence > 95 and > 90%, respectively, during the fourth quarter, versus 59.8 and 75.5% at baseline). A statistically significant decrease in viral load and increase in CD4 cells was seen following program application. The percentage of patients with a viral load < 200 copies/ml was 72.2, 76.7, and 75.0% at the 2nd, 3rd, and 4th quarters, respectively, versus 64.2% at baseline. CD4 cell counts increased by 50 cells/mm3 on average from the start to the end of follow-up. CONCLUSIONS: Patients included in the program had a good immunologic and virologic outcome, and a trend towards an increased percentage of patients with good adherence was also seen. These results confirm the need to implement follow-up programs for patients receiving antiretrovirals in order to ensure maximum therapeutic benefits.

[Resistance to antiretroviral therapy]. / Resistencias al tratamiento antirretroviral.

OVERVIEW: After some time under treatment, HIV+ patients have a virologic failure rate of 50%, being development of resistance to therapy responsible for up to 80% of the virologic failure. In addition, resistance rates in naive patients is around 10% in developed countries. Inherent characteristics of HIV (replication cycle, viral subtype), of patients (therapy compliance, intra-/interindividual variability, genetic polymorphisms), and of therapy (genetic barrier to drug resistance, inhibitory ratio, drug interactions) are the factors involved in the development of resistance, and their interpretation requires to be studied. Resistance identification will be carried out using genotypical and/or phenotypical methods, and their adequacy has been validated by various expert panels on resistance. The role of the pharmacokinetic and pharmacodynamic monitoring of antiretroviral therapy is also crucial within the field of resistance, and concerns us directly as pharmacists. Finally, understanding the resistance patterns of currently available or experimental antiretroviral drug families will provide the necessary tools to prevent and/or manage their development. OBJECTIVES: To know and understand the mechanisms and patterns of resistance for each antiretroviral family. To identify factors involved in the development of resistance to ART, and to interpret various resistance tests. SEARCH STRATEGY: Studies were identified using Medline, the Cochrane database of systemic reviews, abstracts from international meetings on AIDS, Conference on Retroviruses and Opportunistic Infections, international meetings on resistance to antiretrovirals, and product monographs from January 1999 to February 2004. SELECTION CRITERIA: To be eligible, studies had to describe viral genome mutations responsible for resistance or hypersusceptibility to ART in relation to precipitating factors. Papers describing resistance identification techniques were also selected. DATA COLLECTION AND ANALYSIS: In all, 1,083 full articles and 64 abstracts and communications at international meetings were retrieved, of which 74 articles and 20 abstracts met the inclusion criteria for our review. PRIMARY RESULTS: Of the 94 reports selected, 86 discussed factors involved in the development of resistance and resistance test interpretation. The remaining 8 reports focused on resistance patterns to the various antiretroviral drug families. Every article described the enzymatic mechanisms induced by mutations responsible for resistance or hypersusceptibility to each antiretroviral family, the classification and nomenclature for each mutation, and the influence of each mutation on the success or failure of patient treatment. REVIEWER S CONCLUSIONS: Knowledge of the mechanisms and patterns of resistance to each antiretroviral family will allow us to overall understand the evolution and outcome of treatment for any given patient. Only thus shall we be able to play an integral role in the therapy of patients.

Evaluación de la integración del farmacéutico en equipos de atención de unidades de hospitalización / Assessing pharmacist integration within health-care teams at hospital units

Objetivo: Describir la integración de un farmacéutico en tres unidades de hospitalización y valorar el impacto clínico y económico de las intervenciones realizadas. Pacientes y método: Participación en la visita diaria a los pacientes ingresados en Medicina Interna y Otorrinolaringología durante 10 meses. Registro diario de las intervenciones y evaluación del impacto de las mismas (clínico y económico).Resultados: Se han registrado 491 intervenciones con un 96,74 por ciento de aceptación. En el 17,68 por ciento de las intervenciones se ha estimado que la eficacia del tratamiento ha mejorado y en el 45,43 por ciento que la toxicidad ha disminuido. La estimación del ahorro generado ha sido de 15.227.668 ptas. (91,520 ¤).Conclusiones: La presencia del farmacéutico en la unidad de hospitalización facilita la relación con el equipo médico y de enfermería, así como la detección y resolución de problemas relacionados con los medicamentos, con el consiguiente ahorro económico. Todo ello justifica la presencia del farmacéutico en las unidades de hospitalización (AU)

Revisión clínica de la utilización de los bifosfonatos / Clinical review of diphosphonate use

Los bifosfonatos son un conjunto de fármacos análogos a la molécula de pirofosfato que por tener gran afinidad por el fosfato cálcico en fase sólida se unen a la hidroxiapatita del hueso, inhibiendo la resorción ósea. Son fármacos que por vía oral se absorben con dificultad, siendo su biodisponibilidad tan sólo del 1-10 por ciento. Su avidez por el hueso hace que el 20-80 por ciento de la dosis absorbida se fije a él, y una vez fijados en el hueso su semivida de eliminación es superior a los diez años. Resisten la hidrólisis, por lo que se eliminan sin metabolizar por vía renal. En general se toleran bien, siendo sus principales efectos adversos los problemas gastrointestinales y/o fiebre. Son el tratamiento de elección en la enfermedad de Paget. Se utilizan también en el tratamiento de metástasis óseas tanto en pacientes con niveles de calcio sérico normal como en presencia de hipercalcemia de causa tumoral, y constituyen uno de los tratamientos básicos de la osteoporosis. Aunque queden muchos aspectos referentes al mecanismo de acción por esclarecer, parece que aportan un considerable beneficio en la calidad de vida de los pacientes tratados. (AU)