Micafungin pharmacokinetic/pharmacodynamic adequacy for the treatment of invasive candidiasis in critically ill patients on continuous venovenous haemofiltration

Emilio Maseda, Santiago Grau, Maria Jose Villagran, Carmen Hernandez-Gancedo, Araceli Lopez-Tofiño, Jason A. Roberts, Lorenzo Aguilar, Sonia Luque, David Sevillano, Maria Jose Gimenez, Fernando Gilsanz

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Abstract

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 ± 15.87 versus 71.31 ± 14.24; P = 0.008) and Day 2 (119.01 ± 27.20 versus 104.54 ± 21.23; 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. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
Original languageEnglish
Pages (from-to)1624-1632
JournalJournal of Antimicrobial Chemotherapy
Volume69
Issue number6
DOIs
Publication statusPublished - 1 Jan 2014

Keywords

  • Candida albicans
  • Candida glabrata
  • Candida parapsilosis
  • Intensive care units

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    Maseda, E., Grau, S., Villagran, M. J., Hernandez-Gancedo, C., Lopez-Tofiño, A., Roberts, J. A., Aguilar, L., Luque, S., Sevillano, D., Gimenez, M. J., & Gilsanz, F. (2014). Micafungin pharmacokinetic/pharmacodynamic adequacy for the treatment of invasive candidiasis in critically ill patients on continuous venovenous haemofiltration. Journal of Antimicrobial Chemotherapy, 69(6), 1624-1632. https://doi.org/10.1093/jac/dku013