Isavuconazole use and TDM in real-world pediatric practice.

Isavuconazole (ISA) is approved for treating invasive aspergillosis and mucormycosis in adults, but its use in children remains off-label. We report on the use of ISA in real-world pediatric practice with 15 patients receiving ISA for treatment of invasive fungal infections. Therapeutic drug monitoring (TDM) was performed in all patients, with 52/111 (46.8%) Ctrough determinations out of range, thus supporting the need for TDM in children, especially those receiving extracorporeal membrane oxygenation (ECMO).

Evidencia científica de la duración del tratamiento antibiótico en las infecciones intraabdominales con control de foco quirúrgico / Scientific evidence of the duration of antibiotic treatment in intra-abdominal infections with surgical focus control

El aumento progresivo de las resistencias antibióticas apremia el tener estrategias para disminuir la presión sobre la microbiota. La duración del tratamiento antibiótico empírico es variable, a pesar de las recomendaciones de las guías. Se ha realizado una revisión bibliográfica de la evidencia científica publicada sobre la duración del tratamiento antibiótico empírico en las infecciones intraabdominales quirúrgicas con control de foco efectivo. Se analizan las guías americanas realizadas por Mazuski et al. de 2017 como eje central en las recomendaciones de la duración de tratamiento antibiótico empírico en infecciones intraabdominales con control del foco y se añade una búsqueda bibliográfica de todos los artículos que contuviesen las palabras claves en Pubmed y Google Scholar. Se recopilan 21 artículos referentes en la duración del tratamiento antibiótico empírico en la infección intraabdominal con control del foco. Con las guías americanas y estos artículos se ha elaborado una propuesta de duración del tratamiento antibiótico empírico en pacientes sin factores de riesgo entre 24 y 72 h. Y en los que presentan factores de riesgo se habría de individualizar el mismo con monitorización activa cada 24 h de fiebre, íleo paralítico y leucocitosis, ante una detección precoz de complicaciones o de necesidad de cambios en el espectro antibiótico. Los tratamientos cortos son igual de eficaces que los de duraciones más prolongadas y se asocian a menos tasa de efectos adversos, por tanto, ajustar y revaluar diariamente la duración del tratamiento antibiótico empírico es fundamental para una mejor praxis (AU)

A non-systematic review of the published scientific evidence has been carried out on the duration of empirical antibiotic treatment in surgical intra-abdominal infections with effective focus control. Given the progressive increase in antibiotic resistance, it is urgent to have strategies to reduce the pressure on the microbiota. The American guidelines made by Mazuski et al. of 2017, as the central axis in the recommendations of the duration of empirical antibiotic treatment in intra-abdominal infections with control of the focus and a bibliographic search of all the articles that contained the keywords in Pubmed and Google Scholar is added. 21 articles referring to the duration of empirical antibiotic treatment in intra-abdominal infection with control of the focus are collected. With the American guidelines and these articles, a proposal is prepared for the duration of empirical antibiotic treatment in patients without risk factors between 24 and 72h. And in those who present risk factors, it should be individualized with active monitoring every 24h of fever, paralytic ileus and leukocytosis, before an early detection of complications or the need for changes in antibiotic treatment. Short treatments are just as effective as those of longer durations and are associated with fewer adverse effects, therefore, daily adjusting and reassessing the duration of empirical antibiotic treatment is essential for better practice (AU)

Scientific evidence of the duration of antibiotic treatment in intra-abdominal infections with surgical focus control.

A non-systematic review of the published scientific evidence has been carried out on the duration of empirical antibiotic treatment in surgical intra-abdominal infections (IIA) with effective focus control. Given the progressive increase in antibiotic resistance, it is urgent to have strategies to reduce the pressure on the microbiota. The American guidelines made by Mazuski et al. of 20171, as the central axis in the recommendations of the duration of empirical antibiotic treatment in intra-abdominal infections with control of the focus and a bibliographic search of all the articles that contained the keywords in Pubmed and Google Scholar is added. 21 articles referring to the duration of empirical antibiotic treatment in intra-abdominal infection with control of the focus are collected. With the American guidelines and these articles, a proposal is prepared for the duration of empirical antibiotic treatment in patients without risk factors between 24 and 72 h. And in those who present risk factors, it should be individualized with active monitoring every 24 h of fever, paralytic ileus and leukocytosis (FIL), before an early detection of complications or the need for changes in antibiotic treatment. Short treatments are just as effective as those of longer durations and are associated with fewer adverse effects, therefore, daily adjusting and reassessing the duration of empirical antibiotic treatment is essential for better practice.

Posicionamiento y actitudes de manejo sobre la profilaxis antifúngica en el paciente hematológico (proyecto PROMIC) / Consensus opinion on antifungal prophylaxis in haematologic patients: Results of the PROMIC project

Introducción. La enfermedad fúngica invasora (EFI) es una importante causa de morbimortalidad en pacientes hematológicos. La profilaxis antifúngica (PAF) está indicada en muchos episodios de este grupo de pacientes. El objetivo de este trabajo fue alcanzar un consenso sobre el abordaje profiláctico de las EFI en el paciente hematológico con el fin de optimizar su manejo. Métodos. Un comité de expertos en hematología y enfermedades infecciosas planteó un cuestionario de 79 ítems con aspectos controvertidos sobre la profilaxis antifúngica en el paciente hematológico. El cuestionario fue evaluado en dos rondas por un panel de expertos siguiendo una metodología Delphi modificada. Resultados. El cuestionario fue respondido por 44 expertos en hematología y enfermedades infecciosas. Tras dos rondas de evaluación se consensuaron 48 ítems en el acuerdo (60,7%) y 19 en el desacuerdo (24%) por lo que hubo consenso en 67 de los 79 ítems planteados (84,8%). Se consensuaron los perfiles de pacientes candidatos a profilaxis y se dilucidaron cuestiones relacionadas con indicaciones, mecanismos de acción, espectro de actividad, toxicidad e interacciones de los antifúngicos. Se analizó particularmente la utilidad de micafungina como profilaxis de EFI. Se consensuó que micafungina es un antifúngico a considerar en este contexto. Puede presentar ventajas sobre otros antifúngicos por su seguridad y menor potencial de interacciones. Conclusiones. Se encontró un alto nivel de consenso en el manejo de la profilaxis de la EFI en el paciente hematológico. Este consenso ofrece indicaciones prácticas sobre su manejo óptimo y puede ayudar a determinar el perfil de los pacientes idóneos a recibir este tipo de intervención (AU)

Introduction. Invasive fungal disease (IFD) is an important cause of morbidity and mortality in haematological patients. Antifungal prophylaxis (AFP) is indicated for a number of clinical scenarios in this group of patients. The aim of this study was to reach a consensus on IFD prophylaxis in haematological patients in order to optimize their management. Methods. A committee of experts in haematology and infectious diseases compiled a survey of 79 items with controversial aspects about antifungal prophylaxis in haematological patients. The survey was evaluated in two rounds by a panel of experts following a modified Delphi methodology. Results. Forty-four experts in haematology and infectious diseases answered the survey. After two evaluation rounds, consensus was reached in 67 of the 79 items (84.8%), specifically 48 items were consensually agreed on (60.7%) and 19 were disagreed on (24.0%). Consensus was reached on prophylaxis candidates profiles and questions related to indications, mechanisms of action, spectrum of activity, toxicity and interactions of antifungal were elucidated. The usefulness of micafungin in IFD prophylaxis was particularly analysed. The consensus reached was that micafungin is an antifungal to be considered in this context as its safety profile and lower interaction potential may be advantageous. Conclusions. A broad consensus was found in the management of IFD prophylaxis in the haematological patient. This consensus provides practical indications about its optimal management and can help determine the profile of patients eligible for this type of intervention (AU)

Cost-effectiveness Analysis of Rivaroxaban versus Acenocoumarol in the Prevention of Stroke in Patients with Non-valvular Atrial Fibrillation in Spain.

Objective: The aim of this study was to evaluate, from the Spanish National Health System perspective, the cost-effectiveness of rivaroxaban (20 mg/day) versus use of acenocoumarol (5 mg/day) for the treatment of patients with non-valvular atrial fibrillation (NVAF) at moderate to high risk for stroke. Methods: A Markov model was designed and populated with local cost estimates, efficacy and safety of rivaroxaban in stroke prevention in NVAF compared with adjusted-dose warfarin clinical results from the pivotal phase III ROCKET AF trial and utility values obtained from the literature. Warfarin and acenocoumarol were assumed to have therapeutic equivalence. Results: Rivaroxaban treatment was associated with fewer ischemic strokes and systemic embolisms (0.289 vs. 0.300 events), intracranial bleeds (0.051 vs. 0.067), and myocardial infarctions (0.088 vs. 0.102) per patient compared with acenocoumarol. Over a lifetime time horizon, rivaroxaban led to a reduction of 0.041 life-threatening events per patient, and increases of 0.103 life-years and 0.155 quality-adjusted lifeyears (QALYs) versus acenocoumarol treatment. This resulted in an incremental cost-effectiveness ratio of €7045 per QALY and €10 602 per life-year gained. Sensitivity analysis indicated that these results were robust and that rivaroxaban is cost-effective compared with acenocoumarol in 89.4% of cases should a willingness-to-pay threshold of €30 000/QALY gained be considered. Conclusions: The present analysis suggests that rivaroxaban is a cost-effective alternative to acenocoumarol therapy for the prevention of stroke and systemic embolisms in patients with NVAF in the Spanish healthcare setting.

[Differential pharmacokinetic characteristics of micafungin. Experience in special populations]. / Características farmacocinéticas diferenciales de micafungina. Experiencia en poblaciones especiales.

Currently, three echinocandins are available for the treatment of fungal infections. Micafungin is the latest drug to be incorporated into this group of antifungal agents. Although the mechanism of action of micafungin is similar to that of other echinocandins, this molecule has certain pharmacokinetic characteristics that distinguish it from other drugs in this group. Nowadays, there is wide information on the pharmacokinetic behavior of micafungin, mainly from patients included in clinical trials. However, there is far less knowledge of the pharmacokinetics of this echinocandin in special populations. The aim of the current review was to analyze the available information on the pharmacokinetics of micafungin in pediatric patients, the elderly, patients with renal insufficiency or liver failure, and transplant recipient.

Características farmacocinéticas diferenciales de micafungina. Experiencia en poblaciones especiales / Differential pharmacokinetic characteristics of micafungin. Experience in special populations

Resumen En la actualidad se dispone de 3 equinocandinas para el tratamiento de infecciones fúngicas. Micafungina ha representado la última incorporación a este grupo de antifúngicos. A pesar de presentar un mecanismo de acción similar, esta molécula tiene algunas características farmacocinéticas distintas a las del resto del grupo. Hoy en día se dispone de amplia información acerca del comportamiento farmacocinético de micafungina procedente, fundamentalmente, de los pacientes incluidos en los ensayos clínicos. Sin embargo, el conocimiento de la farmacocinética de esta equinocandina en poblaciones especiales es mucho más limitado. El objetivo de la presente revisión es analizar la información disponible sobre la farmacocinética de micafungina en pediatría, pacientes ancianos, insuficiencia renal, insuficiencia hepática y en pacientes trasplantados (AU)

Currently, three echinocandins are available for the treatment of fungal infections. Micafungin is the latestdrug to be incorporated into this group of antifungal agents. Although the mechanism of action ofmicafungin is similar to that of other echinocandins, this molecule has certain pharmacokineticcharacteristics that distinguish it from other drugs in this group. Nowadays, there is wide information onthe pharmacokinetic behavior of micafungin, mainly from patients included in clinical trials. However,there is far less knowledge of the pharmacokinetics of this echinocandin in special populations. The aim ofthe current review was to analyze the available information on the pharmacokinetics of micafungin inpediatric patients, the elderly, patients with renal insufficiency or liver failure, and transplant recipient

[Pharmacoeconomics of therapy in invasive candidiasis]. / Farmacoeconomía del tratamiento de las candidiasis invasoras.

BACKGROUND: Invasive candidiasis episodes have increased during last years and they have been related with high rates of crude mortality. Invasive candidiasis-related deaths have not diminished significantly with the introduction of antifungals in the past decade. Finantial managers are worried about extra costs from acquisition of new antifungal agents. AIM: This review includes the main studies age-stratified to assess different variables related to the economic burden of invasive candidiasis. METHODS: Systematic review of biomedic databases including Medline, PubMed and EMBASE. RESULTS: The studies show hospital stay as the main variable related with higher impact in the increase of invasive candidiasis costs. Acquisition costs of antifungals have a very low impact in the invasive candidiasis costs. CONCLUSIONS: Pharmacoeconomics applied in candidiasis invasive therapy must avoid assessing acquisition costs of antifungals exclusively, needing to include both direct and indirect costs associated with this fungal infection. The cost of antifungal acquisition represents a low impact in the overall economic burden of this fungal infection. Further pharmacoeconomics evaluations should be performed including similar definitions to decrease the possible bias in results interpretation.

Farmacoeconomía del tratamiento de las candidiasis invasoras / Pharmacoeconomics of therapy in invasive candidiasis

Antecedentes: Con los años, los episodios de candidiasis invasora se han incrementado y se han asociado con ratios elevados de mortalidad bruta. Los antifúngicos introducidos durante la pasada década no han producido una disminución significativa de la mortalidad relacionada con esta enfermedad infecciosa. Los costes de adquisición de los antifúngicos suponen una gran preocupación en la gestión de los costes de farmacia. Objetivos: Desarrollar una revisión de los principales estudios efectuados, estratificados por grupos de edad, para evaluar las distintas variables que afectan a la carga económica, así como los costes ocasionados por la candidiasis invasora. Métodos: Búsqueda sistemática de bases de datos Medline, PubMed y EMBASE. Resultados: Los estudios efectuados en pacientes con candidiasis invasora muestran que la estancia hospitalaria es la variable con más impacto en el incremento de los costes relacionados con esta infección fúngica. El coste de adquisición de los antifúngicos representa un porcentaje muy inferior al de otras variables analizadas. Conclusiones: El análisis farmacoeconómico de la candidiasis invasora requiere la inclusión del estudio de los costes directos e indirectos que lleva asociados, y no tan sólo, el de los costes de adquisición de los antifúngicos. Estos últimos representan una pequeña parte del coste total de esta enfermedad. Es preciso efectuar nuevos análisis farmacoeconómicos que unifiquen las definiciones utilizadas en los estudios con el fin de disminuir su impacto en la interpretación de los resultados (AU)

Background: Invasive candidiasis episodes have increased during last years and they have been related with high rates of crude mortality. Invasive candidiasis-related deaths have not diminished significantly with the introduction of antifungals in the past decade. Finantial managers are worried about extra costs from acquisition of new antifungal agents. Aim: This review includes the main studies agestratified to assess different variables related to the economic burden of invasive candidiasis. Methods: Systematic review of biomedic databases including Medline, PubMed and EMBASE. Results: The studies show hospital stay as the main variable related with higher impact in the increase of invasive candidiasis costs. Acquisition costs of antifungals have a very low impact in the invasive candidiasis costs. Conclusions: Pharmacoeconomics applied in candidiasis invasive therapy must avoid assessing acquisition costs of antifungals exclusively, needing to include both direct and indirect costs associated with this fungal infection. The cost of antifungal acquisition represents a low impact in the overall economic burden of this fungal infection. Further pharmacoeconomics evaluations should be performed including similar definitions to decrease the possible bias in results interpretation (AU)