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Infeccions nosocomials; Hospitals; Vigilància epidemiològica Infecciones nosocomiales; Hospitales; Vigilancia epidemiológica Nosocomial infections; Hospitals; Epidemiological surveillance VINCat és un programa que estableix un sistema de vigilància unificat de les infeccions nosocomials als hospitals de Catalunya. La seva missió és contribuir a reduir les taxes d'aquestes infeccions mitjançant la vigilància epidemiològica activa i continuada. El programa es fonamenta en la tasca que porten a terme els professionals dels equips multidisciplinaris de control d'infecció dels hospitals catalans. VINCat is a program of the Catalan Health Service that establishes a unified surveillance system for nosocomial infections in hospitals in Catalonia. Its mission is to help reduce the rates of these infections through active and ongoing epidemiological surveillance. The program is based on the work carried out by the multidisciplinary teams of infection control of Catalan hospitals. VINCat es un programa del Servicio Catalán de la Salud que establece un sistema de vigilancia unificado de las infecciones nosocomiales en los hospitales de Cataluña. Su misión es contribuir a reducir las tasas de estas infecciones mediante la vigilancia epidemiológica activa y continuada. El programa se fundamenta en la tarea que llevan a cabo los profesionales de los equipos multidisciplinares de control de infección de los hospitales catalanes.

Therapeutic drug monitoring of infliximab can guide clinical decisions in patients with loss of response and in those who can benefit from a de-intensification. The aim of this study was to determine the impact of therapeutic drug monitoring combined with Bayesian forecasting methodology on clinical response in a real-world dataset of patients suffering from inflammatory bowel disease.We performed a single-centre prospective study with one-group pre-test/post-test design in 108 adult inflammatory bowel disease patients treated with model-based dosing of infliximab maintenance treatment. We recorded clinical activity scores (Harvey-Bradshaw index and partial Mayo) and inflammatory biomarkers per patient.The initial infliximab regimen was maintained in 49 (45.4%) patients and was adjusted in 59 (54.6%) patients (34 treatment intensifications, 9 de-intensifications and 16 treatment discontinuations or therapy replacements). The median time from intervention to index measurement was 126 (103-160) days. The overall proportion of patients in clinical remission increased from 65.7% to 80.4% (P.0001) and the median infliximab trough concentrations increased from 3.21 (0.99-5.45) to 5.13 mg/L (3.57-6.53) (P.0001). In the intensified group, the remission rate increased from 35.3% to 61.8% (P = .001) and the percentage of patients in clinical remission or with mild symptoms increased from 76.5% to 94.1%. In the de-intensification cohort, no patients experienced an increase in the Harvey-Bradshaw index or partial Mayo scores, and all patients maintained an infliximab trough concentration of5 mg/L.In our cohort of inflammatory bowel disease patients, Bayes-based optimized dosing improved the short-term efficacy of infliximab treatment.

Morbidity and mortality from serious infections are common in intensive care units (ICUs). The appropriateness of the antibiotic treatment is essential to combat sepsis. We aimed to evaluate pharmacokinetic/pharmacodynamic target attainment of meropenem and piperacillin/tazobactam administered at standard total daily dose as continuous infusion in critically ill patients without renal dysfunction and to identify risk factors of non-pharmacokinetic/pharmacodynamic target attainment. We included 118 patients (149 concentrations), 47% had microorganism isolation. Minimum inhibitory concentration (MIC) [median (interquartile range, IQR) values in isolated pathogens were: meropenem: 0.05 (0.02–0.12) mg/l; piperacillin: 3 (1–4) mg/l]. Pharmacokinetic/pharmacodynamic target attainments (100%fCss≥1xMIC, 100%fCss≥4xMIC and 100%fCss ≥ 8xMIC, respectively) were: 100%, 96.15%, 96.15% (meropenem) and 95.56%, 91.11%, 62.22% (piperacillin) for actual MIC; 98.11%, 71.70%, 47.17% (meropenem, MIC 2 mg/l), 95.83%, 44.79%, 6.25% (piperacillin, MIC 8 mg/l), 83.33%, 6.25%, 1.04% (piperacillin, MIC 16 mg/l) for EUCAST breakpoint of Enterobacteriaceae spp. and Pseudomonas spp. Multivariable linear analysis identified creatinine clearance (CrCL) as a predictive factor of free antibiotic concentrations (fCss) of both therapies (meropenem [β = − 0.01 (95% CI − 0.02 to − 0.0; p = 0.043)] and piperacillin [β = − 0.01 (95% CI − 0.02 to 0.01, p 8 mg/l. CrCL was the most powerful factor predictive of fCss in both therapies.

La artritis reumatoide (AR) es una enfermedad inflamatoria sistémica crónica que requiere tratamiento a largo plazo. Dado que el daño articular en pacientes con AR habitualmente es progresivo y éstos requieren tratamiento durante largos periodos de tiempo, es necesario un seguimiento a largo plazo para evaluar la eficacia y la seguridad de los tratamientos e intervenciones. Los fármacos biológicos han supuesto un gran avance terapéutico en el tratamiento de las enfermedades inflamatorias inmunomediadas. La European League Against Rheumatism (EULAR) define la falta de respuesta primaria como una reducción ≤0,6 del Disease Activity Score (DAS) en 28 articulaciones, valorando la velocidad de sedimentación glomerular (DAS28‑VSG) inicial tras 12-24 semanas de tratamiento y la pérdida de respuesta secundaria como un aumento en DAS28-VSG >0,6 o un aumento de actividad de la enfermedad. Uno de los pilares del tratamiento de la AR en la actualidad son los inhibidores del factor de necrosis tumoral alfa (iTNFα); sin embargo, se ha descrito que un 33% de los pacientes con AR no responden inicialmente a estos fármacos, y hasta el 30% pierden la respuesta clínica inicial con el tiempo. Esta variabilidad e incapacidad de predecir la respuesta a los iTNFα se ha descrito como intrínseca a la terapia biológica para la AR. Identificar a los pacientes con mayor probabilidad de presentar pérdida de respuesta, tanto primaria como secundaria, podría permitir que un número significativo de ellos alcanzara su objetivo terapéutico realizando los ajustes adecuados. Así, el objetivo principal de este estudio es la revisión de la evidencia que incluya información sobre las causas de falta o pérdida de respuesta, así como de los factores que influyen en la predicción de la respuesta a los iTNFα en la AR. Palabras clave: Artritis reumatoide, agente biológico, monitorización farmacocinética.

Introduction: Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin against S. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia. Methods: We will perform a superiority, randomised, open-label, phase IV-III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (≥18 years) with isolation of MSSA from at least one blood culture ≤72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician. Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation). We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant). Ethics and dissemination: Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders.

Background The pharmacokinetics (PK) of antibiotics change during sepsis and continuous renal replacement therapies in critically ill patients. Limited evidence exists on the use of the oXiris® high-adsorbent membrane. Objectives To develop a PK/pharmacodynamic (PD) model for meropenem in critically ill sepsis patients undergoing continuous venovenous haemodiafiltration (CVVHDF) with the oXiris® membrane, and to design an optimal dosing regimen assessed according to the PTA. Methods A prospective, open-label, observational PK trial was performed (EUDRACT 2011-005902-30). We conducted PK studies (plasma and ultrafiltrate) for at least 24 h after concomitant administration of CVVHDF and meropenem 1 g q8h. We constructed a PK model using the non-linear mixed-effects approach (NONMEM 7.3). We evaluated the suitability of different dosage regimens using Monte Carlo simulations and calculated the PTA as the percentage of subjects achieving a given percentage of time above the MIC (fT>MIC). Results The PK of meropenem was best captured by a two-open-compartment model with zero-order input kinetics and first-order elimination. Extracorporeal CL was 7.78 L/h [relative standard error (RSE) 16.45 L/h] and central compartment V (Vc) was 24.9 L (RSE 13.73 L). Simulations showed that, for susceptible Pseudomonas aeruginosa isolates (EUCAST MIC ≤2 mg/L) and attainment of 100%fT>MIC, 500 mg q8h given as extended (EI) or continuous infusion (CI) would be sufficient. For a target of 100%fT>4×MIC, CI of 3000 mg q24h or 2000 mg q8h administered as EI or CI would be required. Conclusions We have constructed a PK model of meropenem in sepsis patients undergoing CVVHDF using the oXiris® membrane. This tool will support physicians when calculating the optimal initial dose.

Morbidity and mortality from serious infections are common in intensive care units (ICUs). The appropriateness of the antibiotic treatment is essential to combat sepsis. We aimed to evaluate pharmacokinetic/pharmacodynamic target attainment of meropenem and piperacillin/tazobactam administered at standard total daily dose as continuous infusion in critically ill patients without renal dysfunction and to identify risk factors of non-pharmacokinetic/pharmacodynamic target attainment.We included 118 patients (149 concentrations), 47% had microorganism isolation. Minimum inhibitory concentration (MIC) [median (interquartile range, IQR) values in isolated pathogens were: meropenem: 0.05 (0.02-0.12) mg/l; piperacillin: 3 (1-4) mg/l]. Pharmacokinetic/pharmacodynamic target attainments (100%fCStandard total daily dose of meropenem allowed achieving pharmacokinetic/pharmacodynamic target attainments in ICU patients without renal dysfunction. Higher doses of piperacillin/tazobactam would be needed to cover microorganisms with MIC8 mg/l. CrCL was the most powerful factor predictive of fC

La esclerosis multiple (EM) es la enfermedad autoinmune, inflamatoria, cronica y degenerativa mas prevalente a nivel mundial, cuya forma mas frecuente es la EM remitente recurrente (EMRR). Para el manejo de la EMRR grave se aprobo natalizumab, un anticuerpo monoclonal IgG4 que se une a la integrina 41 de la superficie de los leucocitos, impidiendo que migren al sistema nervioso central. Con la dosis fija intravenosa aprobada, de 300 mg cada 4 semanas, se ha comprobado que mas del 90% de los pacientes alcanzan concentraciones sericas preinfusion de NTZ >10 μg/mL, cuando la eficacia se ha demostrado con unos niveles de 2,5-10 μg/mL. Una concentracion plasmatica de NTZ de 2,5 μg/mL asegura una ocupacion del 50% de la biofase y demuestra una eficacia terapeutica, mientras que tasas de ocupacion del 20-40% se han relacionado con un aumento de la actividad de la enfermedad. Palabras clave: Esclerosis multiple, natalizumab, farmacocinética

Los anticuerpos monoclonales (mAb) representan uno de los grupos terapéuticos de mayor interés en el desarrollo farmacológico. Por toda su complejidad (estructural y funcional), el seguimiento farmacocinético de los fármacos biológicos debería ser imprescindible en la práctica clínica habitual. La absorción de los mAb tras su administración intramuscular o subcutánea se puede producir por vía sanguínea o linfática, y su distribución depende del mecanismo de extravasación, la afinidad del mAb para componentes tisulares y del aclaramiento (Cl) tisular. La eliminación se produce principalmente por proteolisis intracelular tras una endocitosis específica (mediada por receptor) o inespecífica. Por otro lado, la captación y posterior liberación del mAb, la redistribución del flujo sanguíneo por procesos fisiológicos, la formación de complejos y el proceso de reciclaje mediante el receptor de Brambell son los mecanismos fisiológicos que condicionan su variabilidad farmacocinética intraindividual. Además, la inmunogenicidad frente al mAb, el peso del paciente y la cantidad de antígeno diana son los principales factores que afectan a su variabilidad farmacocinética. Palabras clave: Anticuerpo monoclonal, farmacocinética, variabilidad.

Los fármacos biológicos se han convertido en agentes clave para el tratamiento de las enfermedades inflamatorias inmunomediadas (IMID). Sin embargo, la terapia biológica está condicionada por la gran variabilidad farmacocinética (PK) inter/ intraindividual. La monitorización terapéutica (TDM), basada en las concentraciones de fármaco biológico y los anticuerpos antifármaco, es una herramienta apropiada para la optimización del tratamiento de las IMID con el objetivo de individualizar la posología para cada paciente. Así, la determinación de concentraciones plasmáticas de los agentes biológicos, junto con la interpretación de los valores clínicos y analíticos, permitiría una evaluación global del estado del paciente, optimizar la exposición al fármaco y mejorar la respuesta clínica. La monitorización de concentraciones plasmáticas se puede realizar en caso de no respuesta (TDM reactiva) o en caso de remisión para mantener una exposición al fármaco adecuada (TDM proactiva). En este artículo se resume la información disponible sobre la TDM de los agentes biológicos para la optimización del tratamiento de la artritis reumatoide (AR). A pesar de la evidencia disponible sobre la asociación entre las concentraciones séricas de fármacos y el resultado clínico en AR, se requieren más datos PK y de coste-efectividad que permitan obtener más información para consolidar la TDM como una intervención en reumatología. Palabras clave: Artritis reumatoide, agente biológico, monitorización farmacocinética.

Background We aimed to determine whether daptomycin plus fosfomycin provides higher treatment success than daptomycin alone for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis. Methods A randomized (1:1) phase 3 superiority, open-label, and parallel group clinical trial of adult inpatients with MRSA bacteremia was conducted at 18 Spanish hospitals. Patients were randomly assigned to receive either 10 mg/kg of daptomycin intravenously daily plus 2 g of fosfomycin intravenously every 6 hours, or 10 mg/kg of daptomycin intravenously daily. Primary endpoint was treatment success 6 weeks after the end of therapy. Results Of 167 patients randomized, 155 completed the trial and were assessed for the primary endpoint. Treatment success at 6 weeks after the end of therapy was achieved in 40 of 74 patients who received daptomycin plus fosfomycin and in 34 of 81 patients who were given daptomycin alone (54.1% vs 42.0%; relative risk, 1.29 [95% confidence interval, .93-1.8]; P = .135). At 6 weeks, daptomycin plus fosfomycin was associated with lower microbiologic failure (0 vs 9 patients; P = .003) and lower complicated bacteremia (16.2% vs 32.1%; P = .022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) receiving daptomycin plus fosfomycin, and in 4 of 81 patients (4.9%) receiving daptomycin alone (P = .018). Conclusions Daptomycin plus fosfomycin provided 12% higher rate of treatment success than daptomycin alone, but this difference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacteremia, but it was more often associated with adverse events.

Introduction and Aim: Pirfenidone and nintedanib are anti-fibrotic approved treatments for idiopathic pulmonary fibrosis (IPF). Its efficacy and safety in other fibrotic interstitial lung diseases (ILD) is under study in clinical trials. The aim was to analyse the effect of these drugs in non-IPF progressive fibrotic patients that couldn’t be included in these trials. Methods: Multicenter retrospective study of 34 progressive PF non-IPF patients treated with anti-fibrotic drugs. Demographic, clinical data and treatment-related variables were evaluated. The reason to start off-label anti-fibrotic was disease progression with previous therapy and exclusion from clinical trials. Results: Patients with non-IPF progressive PF were: 38% unclassifiable PF (UPF), 20% familial pulmonary fibrosis (FPF), 18% CTD-ILD, 15% chronic hypersensitivity pneumonitis (CHP) and 9% pneumoconiosis. Mean age was 67±12 years, 74% were male and 47% ex-smokers. 21% of cases had usual interstitial pneumonia HRCT pattern. Mean FVC was 66%±23 and DLCO 45%±12. Co-medications were: low-dose prednisone (20), mycophenolate (5) and sirolimus (1). Twenty-four subjects (71%) received pirfenidone and ten (29%) nintedanib. After one year, a FVC decrease of 5-10% was observed in only 3 patients (1 CHP, 1 pneumoconiosis, 1 UPF), while others showed stability or improvement. Main reported adverse effects were: 20% hypertransaminasemia, 27% diarrhea and 15% weight loss, requiring 5 patients to stop therapy. Conclusion: After one year of anti-fibrotic therapy, most patients with non-IPF progressive PF showed functional stability. Clinical trials are mandatory to evaluate their potential efficacy, but these drugs are a safe option in progressive PF patients.

To determine the percentage of patients given standard doses of piperacillin/tazobactam or meropenem by continuous infusion who achieved the target pharmacokinetic/pharmacodynamic (PK/PD) index, which was defined as free concentrations four times more than the minimum inhibitory concentration (CMI) for 100% of the dosing interval (100% fT≥ 4 x MIC).Preliminary data from a larger prospective clinical study analysing the PK/PD behaviour of β-lactams antibiotics continuous infusion (CI) in critical patients. The study was conducted in the intensive care units of a tertiary university hospital for adults (June 2015-May 2017). Inclusion criteria: normal renal function (glomerular renal function (GFR) CKD-EPI formula ≥ 60 mL/min/1.73 m2) and treatment with standard dose β-lactams CI. Concentrations at steady state (Css) conditions were determined using UHPLC-MS/MS. We selected the highest susceptible MIC for all likely organisms according to European Commitee on Antimicrobial Susceptibility Testing's (i.e. piperacillin/tazobactam: 8 mg/L for enterobacteriaceae and 16 mg/L for Pseudomonas aeruginosa; meropenem: 2 mg/L for any microorganism). In addition, a subanalysis of patients was conducted using actual MIC values.61 patients were enrolled (25 to meropenem and 36 to piperacillin/tazobactam). Average age was 59 (15) years and median GFR rate was 95 mL/min/1.73 m2 (83-115). Median meropenem and piperacillin free concentrations were 16 mg/L (11-29) and 40 mg/L (21- 51), respectively. 88% of patients treated with meropenem reached the PK/PD target, without differences between both microorganisms. For piperacillin/tazobactam, 61% and 11% of patients reached the target, with enterobacteriaceae and Pseudomonas as suspected microorganisms, respectively. The pathogen was isolated in 35 (57%) patients: 94% reached the target PK/PD, without differences between both antibiotic therapies.Standard doses of meropenem CI are sufficient to achieve a PK/PD target of 100% fT≥ 4 x MIC in suspected infections with high MICs (Pseudomonas aeruginosa or enterobacteriaceae). However, higher doses of piperacillin/tazobactam could be considered to achieve this goal. In patients with isolated microorganisms, a standard dose of both antibiotic therapies would be sufficient to achieve the target. Therapeutic drug monitoring is highly recommended for therapeutic optimization.Objetivo: Determinar el porcentaje de pacientes, a los que se les administró dosis estándar de piperacilina/tazobactam o meropenem en perfusión continua, que alcanzaban el índice farmacocinético/farmacodinámico diana definido como el 100% del intervalo de administración en que las concentraciones de antibiótico libre fueron cuatro veces iguales o superiores a la concentración mínima inhibitoria (100% fT ≥ 4 x CMI).Método: Datos preliminares obtenidos de un estudio clínico prospectivo que analiza el comportamiento farmacocinético/farmacodinámico de los antibióticos betalactámicos administrados en perfusión continua en pacientes críticos. Se realizó en unidades de cuidados intensivos de un hospital universitario de tercer nivel, desde junio de 2015 a mayo de 2017. Criterios de inclusión: adultos con función renal correcta (filtrado glomerular según la fórmula CKD-EPI ≥ 60 ml/min/1,73 m2) y tratados con dosis estándar de antibióticos betalactámicos en perfusión continua. Las concentraciones en estado de equilibrio estacionario fueron determinadas mediante cromatografía líquida acoplada a espectrometría de masas (UHPLC- MS/MS). Se utilizaron valores de concentración mínima inhibitoria teóricos para microorganismos más resistentes (piperacilina/ tazobactam: 16 mg/l para Pseudomonas aeruginosa y 8 mg/l para Enterobacteriaceae; meropenem: 2 mg/l, independientemente del microorganismo). Además, se realizó un subanálisis de los pacientes con aislamiento microbiológico (concentraciones mínimas inhibitorias reales).Resultados: Se incluyeron 61 pacientes (25 meropenem y 36 piperacilina/ tazobactam). Edad media 59 años (15), mediana de filtrado glomerular 95 ml/min/1,73 m2 (83-115). Mediana de concentraciones en estado de equilibrio estacionario libre: 16 mg/l (11- 29) meropenem y 40 mg/l (21-51) piperacilina. El 88% de los pacientes tratados con meropenem alcanzaron el objetivo farmacocinético/farmacodinámico, sin diferencias entre Enterobacteriaceae y Pseudomonas. En el caso de piperacilina/tazobactam, el 61% y el 11% de los pacientes alcanzaron la diana, considerando Enterobacteriaceae y Pseudomonas como microorganismo sospechoso. Un total de 35 (57%) pacientes presentaron aislamiento microbiológico. El 94% de ellos alcanzaron la diana, sin diferencias entre los dos antibióticos.Conclusiones: Ante la sospecha de infecciones por microorganismos con concentraciones mínimas inhibitorias elevadas (Pseudomonas aeruginosa o enterobacterias), se observa que dosis convencionales de meropenem en perfusión continua son suficientes para lograr la diana 100% fT≥ 4 x MIC. Sin embargo, se requerirían dosis superiores de piperacilina/tazobactam. En casos de aislamiento microbiológico, dosis estándar de ambos antibióticos fueron suficientes para lograr la diana. La monitorización farmacocinética es altamente recomendable para la optimización terapéutica.

INTRODUCTION Most of the cost-effectiveness analyses are based on estimations to make decisions on the future implementation of a test. However, the model should be verified with real data to prove that previous estimations have been successfully fulfilled. OBJECTIVE To study the economic impact of the systematic HLA-B*57:01 genotyping in preventing hypersensitivity reactions (HSRs) in the patient population of a tertiary-care hospital treated with abacavir (ABC) using retrospective data of 5 years of experience. METHODS A retrospective study was carried out with two cohorts including 780 and 473 patients before and after the implementation of the systematic HLA-B*57:01 genotyping before ABC treatment. Cost-effectiveness analysis was carried out by the parameter 'cost per HSR avoided'. The clinical utility of the test was verified by evaluating the differences in HSR incidence between both cohorts. Finally, a sensitivity analysis including all variables was carried out. RESULTS In the population studied, systematic genotyping represents an additional cost of O306 per HSR avoided. In the sensitivity analysis, pharmacological therapy cost is the major influencing factor found in the estimation of the 'cost per HSR avoided'. In terms of clinical utility, the incidence ratio was 0.040 (95% confidence interval 0.0009-0.2399) and statistically significant differences were found between both groups (P=1.40×10). CONCLUSION Retrospective data from 5 years of experience have confirmed the cost-effectiveness of the systematic genotyping in candidate patients for ABC therapy, and have shown that cost-effectiveness is a dynamic parameter closely linked to allele prevalence and pharmacological therapy costs.

Sr. Director: hemos leído con interés el artículo publicado en su revista por Elberdín L et al titulado La monitorización farmacocinética como nueva herramienta para individualizar la terapia anti-TNF1. Nos parece relevante comentar algunos aspectos del tema tratado, con la intención de contribuir a la discusión y ampliarlos, teniendo en cuenta la experiencia en nuestro hospital con la monitorización de Infliximab (IFX) en pacientes afectos de enfermedad inflamatoria intestinal (EII).

Objetivo El deficit de alfa-1-antitripsina (AAT) es una enfermedad genetica autosomica codominante, que predispone a enfermedad pulmonar obstructiva cronica y enfisema. El tratamiento especifico consiste en la administracion intravenosa sistematica de AAT. La pauta de tratamiento actual recomendada por el Registro Espanol es de 180 mg/kg cada 21 dias. El objetivo de este trabajo ha sido evaluar el comportamiento farmacocinetico de la AAT y estimar el grado de cobertura, definido como el porcentaje de tiempo que la concentracion plasmatica de AAT se situa en valores superiores a 50 mg/dl, valor considerado como protector, de la pauta de tratamiento habitual y otras pautas alternativas. Material y metodos El analisis farmacocinetico de la AAT se realizo mediante el ajuste de 4 pares de valores concentracion/ tiempo, de 9 pacientes, a un modelo farmacocinetico monocompartimental abierto empleando el paquete informatico Win-Nonlin. La estimacion del tiempo de cobertura se efectuo mediante la simulacion de la evolucion de la actividad plasmatica de la AAT, en funcion del tiempo, segun el modelo propuesto y los valores de los parametros obtenidos en el estudio. Resultados Los pacientes presentaban las caracteristicas demograficas siguientes: 5 varones y 4 mujeres, peso medio de 69 kg (intervalo, 59-84 kg) y dosis media de AAT por infusion de 12,06 g (intervalo, 11-15 g). El volumen medio (± desviacion estandar) de infusion fue de 516,67 ± 88,17 ml. La vida media de la AAT fue de 8,7 dias, y el volumen de distribucion de 127,6 ml/kg. La pauta de tratamiento actual (180 mg/kg cada 21 dias) presento un porcentaje de cobertura del 67% (considerando que 60 mg/dl es el valor protector) o del 76% (para 50 mg/dl), y los porcentajes para la pauta alternativa de 120 mg/kg cada 14 dias fueron del 82 y el 100%, respectivamente. Para 60 mg/kg cada 7 dias fue del 100% en ambos casos. Conclusiones La caracterizacion del comportamiento farmacocinetico de la AAT ha permitido evaluar el tiempo de cobertura de las diversas pautas de tratamiento y establecer como mas adecuada la de 120 mg/kg cada 14 dias.

Objective α1-antitrypsin (AAT) deficiency is a codominant autosomal genetic disorder that predisposes a patient to chronic obstructive pulmonary disease and emphysema. Specific treatment is systemic, consisting of intravenous infusion of AAT. The protocol currently recommended by the Spanish Registry is infusion of 180 mg/kg every 21 days. The objective of this study was to assess the pharmacokinetic behavior of AAT and estimate the level of protection, defined as the percentage of time that the AAT plasma concentration was above the assumed protective threshold of 50 mg/dL with the usual protocol and with other alternative ones. Material and Methods Plasma concentrations at 4 times were analyzed for 9 patients to profile the pharmacokinetics of AAT. The data were fitted to a single compartment open model with the WinNonlin software package. The duration of protection was estimated by simulating the evolution of AAT plasma activity over time according to the model constructed based on data recorded in the study. Results Five men and 4 women (mean weight, 69 kg; range, 59-84 kg) were given a mean AAT dose of 12.06 g (range, 11-15 g). The mean (SD) volume infused was 516.67 (88.17) mL. The half-life of AAT was 8.7 days and the volume of distribution was 127.6 mL/kg. The currently recommended treatment protocol (180 mg/kg every 21 days) gave a level of protection of 67% (considering 60 mg/dL to be protective threshold) or 76% (for a threshold of 50 mg/dL). Protection values for the alternative protocol of 120 mg/kg every 14 days were 82% and 100%, respectively. For the alternative protocol of 60 mg/kg every 7 days, protection was 100% for both thresholds. Conclusions Profiling the pharmacokinetic behavior of AAT has enabled the coverage time to be assessed for several treatment protocols. The regimen of 120 mg/kg every 14 days had the most appropriate profile.

Objectives To analyse the possible relationship between consumption of old and new MRSA-active antibiotics and burden of MRSA in acute care hospitals in Catalonia during the period 2007–12. Methods Fifty-four hospitals participating in the VINCat Programme were included. Proportion of MRSA (resistant isolates of Staphylococcus aureus per 100 isolates of S. aureus tested), incidence of new cases of infection [new cases of MRSA per 1000 occupied bed-days (OBD)] and incidence of cases of bacteraemia (MRSA bacteraemia cases per 1000 OBD) were determined to estimate the annual MRSA burden. Antibiotic consumption was calculated in DDD/100 OBD. Cost was expressed in euros/100 OBD. Results MRSA rates remained stable over the study period, with the proportion of MRSA ranging from 20% to 22.82% in 2007 and 2012, respectively (P = 0.864). Consumption of old MRSA-active antibiotics (vancomycin and teicoplanin) did not change significantly, with values from 1.51 to 2.07 DDD/100 OBD (P = 0.693). Consumption of new MRSA-active antibiotics (linezolid and daptomycin) increased significantly, with values rising from 0.24 to 1.49 DDD/100 OBD (P Conclusions A widespread and steady increase in consumption of new MRSA-active antibiotics was observed among acute care hospitals in Catalonia, in spite of a stable MRSA burden. At the same time, consumption of old drugs remained stable. Such trends resulted in a significant increase in cost. Our findings suggest that factors other than the proportion of methicillin resistance among S. aureus may influence the use of old and new MRSA-active antibiotics in the clinical setting.