title: Micafungin pharmacokinetic/pharmacodynamic adequacy for the treatment of invasive candidiasis in critically ill patients on continuous venovenous haemofiltration.
abstract: OBJECTIVE
  To explore the pharmacokinetics (PK) and pharmacodynamics (PD) of micafungin in patients undergoing continuous venovenous haemofiltration (CVVH).
  
  
  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.
authors: Anaesthesiology and Surgical Critical Care Department, Hospital La Paz, Madrid, Spain emilio.maseda@gmail.com.
authors: Emilio
authors: E
authors: Maseda
authors: Pharmacy Department, Hospital del Mar, Barcelona, Spain Universitat Autònoma de Barcelona, Barcelona, Spain.
authors: Santiago
authors: S
authors: Grau
authors: Anaesthesiology and Surgical Critical Care Department, Hospital La Paz, Madrid, Spain.
authors: Maria-Jose
authors: MJ
authors: Villagran
authors: Anaesthesiology and Surgical Critical Care Department, Hospital La Paz, Madrid, Spain.
authors: Carmen
authors: C
authors: Hernandez-Gancedo
authors: Anaesthesiology and Surgical Critical Care Department, Hospital La Paz, Madrid, Spain.
authors: Araceli
authors: A
authors: Lopez-Tofiño
authors: Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
authors: Jason A
authors: JA
authors: Roberts
authors: Microbiology Unit, Medicine Department, School of Medicine, Universidad Complutense, Madrid, Spain.
authors: Lorenzo
authors: L
authors: Aguilar
authors: Pharmacy Department, Hospital del Mar, Barcelona, Spain.
authors: Sonia
authors: S
authors: Luque
authors: Microbiology Unit, Medicine Department, School of Medicine, Universidad Complutense, Madrid, Spain.
authors: David
authors: D
authors: Sevillano
authors: Microbiology Unit, Medicine Department, School of Medicine, Universidad Complutense, Madrid, Spain.
authors: Maria-Jose
authors: MJ
authors: Gimenez
authors: Anaesthesiology and Surgical Critical Care Department, Hospital La Paz, Madrid, Spain.
authors: Fernando
authors: F
authors: Gilsanz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002175:Candida / Q000187:drug effects*; D058365:Candidiasis, Invasive / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology; D016638:Critical Illness / Q000628:therapy*; D054714:Echinocandins / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006440:Hemofiltration / Q000009:adverse effects; D006801:Humans; D007362:Intensive Care Units; D055666:Lipopeptides / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D000077551:Micafungin; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009010:Monte Carlo Method
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077551:Micafungin
keywords: Candida albicans; Candida glabrata; Candida parapsilosis; intensive care units