Dosage Individualization of Linezolid: Precision Dosing of Linezolid To Optimize Efficacy and Minimize Toxicity.

The high interindividual variability in the pharmacokinetics (PK) of linezolid has been described, which results in an unacceptably high proportion of patients with either suboptimal or potentially toxic concentrations following the administration of a fixed regimen. The aim of this study was to develop a population pharmacokinetic model of linezolid and use this to build and validate alogorithms for individualized dosing. A retrospective pharmacokinetic analysis was performed using data from 338 hospitalized patients (65.4% male, 65.5 [±14.6] years) who underwent routine therapeutic drug monitoring for linezolid. Linezolid concentrations were analyzed by using high-performance liquid chromatography. Population pharmacokinetic modeling was performed using a nonparametric methodology with Pmetrics, and Monte Carlo simulations were employed to calculate the 100% time >MIC after the administration of a fixed regimen of 600 mg administered every 12 h (q12h) intravenously (i.v.). The dose of linezolid needed to achieve a PTA ≥ 90% for all susceptible isolates classified according to EUCAST was estimated to be as high as 2,400 mg q12h, which is 4 times higher than the maximum licensed linezolid dose. The final PK model was then used to construct software for dosage individualization, and the performance of the software was assessed using 10 new patients not used to construct the original population PK model. A three-compartment model with an absorptive compartment with zero-order i.v. input and first-order clearance from the central compartment best described the data. The dose optimization software tracked patients with a high degree of accuracy. The software may be a clinically useful tool to adjust linezolid dosages in real time to achieve prespecified drug exposure targets. A further prospective study is needed to examine the potential clinical utility of individualized therapy.

Population Pharmacokinetics of Anidulafungin in Critically Ill Patients.

A two-compartment pharmacokinetic (PK) population model of anidulafungin was fitted to PK data from 23 critically ill patients (age, 65 years [range, 28 to 81 years]; total body weight [TBW], 75 kg [range, 54 to 168 kg]). TBW was associated with clearance and incorporated into a final population PK model. Simulations suggested that patients with higher TBWs had less-extensive MIC coverage. Dosage escalation may be warranted in patients with high TBWs to ensure optimal drug exposures for treatment of Candida albicans and Candida glabrata infections.

Active humidification in mechanical ventilation is not associated to an increase in respiratory infectious complications in a quasi-experimental pre-post intervention study.

OBJECTIVE: There is controversy regarding the influence of humidification systems upon the incidence of respiratory infections associated to invasive mechanical ventilation (IMV). An evaluation was made of the differences in the incidence of pneumonia and tracheobronchitis associated to mechanical ventilation (VAP and VAT, respectively) with passive and active humidification. DESIGN: A retrospective pre-post quasi-experimental study was carried out. SETTING: A polyvalent ICU with 14 beds. PATIENTS: All patients connected to IMV for >48h during 2014 and 2016 were included. INTERVENTIONS: During 2014, passive humidification with an hygroscopic heat and moisture exchanger (HME) was used, while during 2016 active humidification with a heated humidifier (HH) and an inspiratory heated wire was used. Identical measures for the prevention of VAP were established (Zero Pneumonia Project). MAIN OUTCOME MEASURES: The incidence of VAP and VAT was estimated for 1000 days of IMV in both groups, and statistically significant differences were assessed using Poisson regression analysis. RESULTS: A total of 287 patients were included (116 with HME and 171 with HH). The incidence density of VAP per 1000 days of IMV was 5.68 in the HME group and 5.80 in the HH group (p=ns). The incidence density of VAT was 3.41 and 3.26 cases per 1000 days of VMI with HME and HH respectively (p=ns). The duration of IMV was identified as a risk factor for VAP. CONCLUSIONS: In our population, active humidification in patients ventilated for >48h was not associated to an increase in respiratory infectious complications.

Ceftolozane-tazobactam for the treatment of ventilator-associated infections by colistin-resistant Pseudomonas aeruginosa.

The use of colistin for the treatment of multiresistant bacteria has led to the emergence of colistin-resistant strains of Gram-negative bacilli. Treatment of infections caused by these pan-drug-resistant bacteria is difficult owing to the paucity of effective antibiotics. We report two cases of ventilator-associated respiratory infection caused by pan-drug-resistant, colistin-resistant Pseudomonas aeruginosa that were successfully treated with ceftolozane-tazobactam.

La humidificación activa en ventilación mecánica no se asocia con un aumento de complicaciones infecciosas respiratorias en un estudio cuasi-experimental pre-postintervención / Active humidification in mechanical ventilation is not associated to an increase in respiratory infectious complications in a quasi-experimental pre-post intervention study

Objetivo Existen controversias sobre la influencia del sistema de humidificación en la incidencia de infecciones respiratorias asociadas a la ventilación mecánica invasiva (VMI). Nuestro objetivo fue evaluar las diferencias en la incidencia de neumonía y traqueobronquitis asociadas a la ventilación mecánica (NAV y TAV respectivamente) con humidificación pasiva y activa. Diseño Estudio retrospectivo cuasi-experimental de tipo pre-postintervención. Ámbito UCI polivalente de 14 camas. Pacientes Se incluyeron todos los pacientes conectados a la VMI durante>48horas durante los años 2014 y 2016. Intervenciones Durante el año 2014 se empleaba humidificación pasiva con un intercambiador calor-humedad (HME) y, durante 2016, humidificación activa (HH) con calentamiento de la tubuladura inspiratoria. Se establecieron medidas idénticas para la prevención de NAV (proyecto Neumonía Zero). Variables de interés principales Se estimaron tasas de incidencia NAV y TAV por 1.000 días de VMI en ambos grupos y se valoraron diferencias estadísticamente significativas mediante regresión Poisson. Resultados Se incluyeron 287 pacientes (116 con HME y 171 con HH). La densidad de incidencia de NAV por 1.000 días de VMI fue de 5,68 en el grupo de HME y 5,80 en el grupo de HH (p=ns). La densidad de incidencia de TAV fue 3,41 y 3,26 casos por 1.000 días de VMI con HME y HH respectivamente (p=ns). Se identificó como factor de riesgo de NAV la duración de la VMI. Conclusiones En nuestro estudio la humidificación activa en pacientes ventilados durante>48horas no se asoció con un aumento de las complicaciones infecciosas respiratorias. (AU)

Objective There is controversy regarding the influence of humidification systems upon the incidence of respiratory infections associated to invasive mechanical ventilation (IMV). An evaluation was made of the differences in the incidence of pneumonia and tracheobronchitis associated to mechanical ventilation (VAP and VAT, respectively) with passive and active humidification. Design A retrospective pre-post quasi-experimental study was carried out. Setting A polyvalent ICU with 14 beds. Patients All patients connected to IMV for>48hours during 2014 and 2016 were included. Interventions During 2014, passive humidification with an hygroscopic heat and moisture exchanger (HME) was used, while during 2016 active humidification with a heated humidifier (HH) and an inspiratory heated wire was used. Identical measures for the prevention of VAP were established (Zero Pneumonia Project). Main outcome measures The incidence of VAP and VAT was estimated for 1000 days of IMV in both groups, and statistically significant differences were assessed using Poisson regression analysis. Results A total of 287 patients were included (116 with HME and 171 with HH). The incidence density of VAP per 1000 days of IMV was 5.68 in the HME group and 5.80 in the HH group (p=ns). The incidence density of VAT was 3.41 and 3.26 cases per 1000 days of VMI with HME and HH respectively (p=ns). The duration of IMV was identified as a risk factor for VAP. Conclusions In our population, active humidification in patients ventilated for>48hours was not associated to an increase in respiratory infectious complications. (AU)

En respuesta a «Vacunación antigripal y protección del paciente crítico: responsabilidad de los profesionales sanitarios» / Reply to «Influenza vaccination and critical patient protection: responsibility of healthcare workers»

No disponible

Successful treatment of Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus pneumonia with high doses of linezolid administered in continuous infusion / Tratamiento eficaz de una neumonia comunitaria producida por un Staphylococcus aureus resitente a meticilina leucocidina Panton-Valantin con altas dosis de linezolid en perfusión continua

No disponible