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Métodos Terapéuticos y Terapias MTCI
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1.
J Antimicrob Chemother ; 69(6): 1624-32, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24505092

RESUMEN

OBJECTIVES: To explore the pharmacokinetics (PK) and pharmacodynamics (PD) of micafungin in patients undergoing continuous venovenous haemofiltration (CVVH). PATIENTS AND METHODS: Ten patients receiving CVVH treated with 100 mg/day micafungin were included (April-December 2012). CVVH was performed using polyethersulphone or polysulphone haemofilters. Dialysis membranes were not changed on sampling days. On Days 1 and 2, blood samples from arterial pre-filter and venous post-filter ports and ultrafiltrate samples were collected at the start and end of the infusion and at 3, 5, 8, 18 and 24 h. Concentrations were determined using HPLC. Values for the area under the concentration-time curve (AUC0-24) were calculated. Monte Carlo simulations were performed using pre-filter and post-filter AUC0-24/MIC ratios on Days 1 and 2. The probability of target attainment (PTA) was calculated using AUC0-24/MIC cut-offs: 285 (C. parapsilosis), 3000 (all Candida spp.) and 5000 (non-parapsilosis Candida spp.). Cumulative fraction responses (CFRs) were calculated using EUCAST MIC distributions. RESULTS: Mean post-filter AUC0-24 (mg·h/L) values were higher than pre-filter values on Day 1 (83.31 ±â€Š15.87 versus 71.31 ±â€Š14.24; P = 0.008) and Day 2 (119.01 ±â€Š27.20 versus 104.54 ±â€Š21.23; P = 0.005). PTAs were ≥90% for MICs of 0.125 mg/L (cut-off = 285), 0.016 mg/L (cut-off = 3000) and 0.008 mg/L (cut-off = 5000) on Day 1, and for MICs of 0.25 mg/L (cut-off = 285) and 0.016 mg/L (cut-off = 3000 and 5000) on Day 2, without differences between pre- and post-filter values. On Day 2, CFRs >90% were obtained for C. albicans (cut-off = 3000 and 5000) and C. glabrata (cut-off = 3000), but not for C. parapsilosis. CONCLUSIONS: There was no removal of micafungin by CVVH or need for dose adjustment, and there was optimal PK/PD coverage for non-parapsilosis Candida and equivalence of pre- and post-filter PD.


Asunto(s)
Antifúngicos/farmacocinética , Candida/efectos de los fármacos , Candidiasis Invasiva/tratamiento farmacológico , Enfermedad Crítica/terapia , Equinocandinas/farmacocinética , Hemofiltración , Lipopéptidos/farmacocinética , Anciano , Anciano de 80 o más Años , Antifúngicos/uso terapéutico , Candidiasis Invasiva/diagnóstico , Candidiasis Invasiva/microbiología , Equinocandinas/uso terapéutico , Femenino , Hemofiltración/efectos adversos , Humanos , Unidades de Cuidados Intensivos , Lipopéptidos/uso terapéutico , Masculino , Micafungina , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Método de Montecarlo
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