Emilio Maseda1, Santiago Grau2, Maria-Jose Villagran3, Carmen Hernandez-Gancedo3, Araceli Lopez-Tofiño3, Jason A Roberts4, Lorenzo Aguilar5, Sonia Luque6, David Sevillano5, Maria-Jose Gimenez5, Fernando Gilsanz3. 1. Anaesthesiology and Surgical Critical Care Department, Hospital La Paz, Madrid, Spain emilio.maseda@gmail.com. 2. Pharmacy Department, Hospital del Mar, Barcelona, Spain Universitat Autònoma de Barcelona, Barcelona, Spain. 3. Anaesthesiology and Surgical Critical Care Department, Hospital La Paz, Madrid, Spain. 4. Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia. 5. Microbiology Unit, Medicine Department, School of Medicine, Universidad Complutense, Madrid, Spain. 6. Pharmacy Department, Hospital del Mar, Barcelona, Spain.
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.
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.
Authors: Vincent J Lempers; Jeroen A Schouten; Nicole G Hunfeld; Angela Colbers; Henk J van Leeuwen; David M Burger; Paul E Verweij; Peter Pickkers; Roger J Brüggemann Journal: Antimicrob Agents Chemother Date: 2015-05-11 Impact factor: 5.191
Authors: M G Vossen; D Knafl; M Haidinger; R Lemmerer; M Unger; S Pferschy; W Lamm; A Maier-Salamon; W Jäger; F Thalhammer Journal: Antimicrob Agents Chemother Date: 2017-07-25 Impact factor: 5.191
Authors: A García-de-Lorenzo; S Luque; S Grau; A Agrifoglio; L Cachafeiro; E Herrero; M J Asensio; S M Sánchez; J A Roberts Journal: Antimicrob Agents Chemother Date: 2016-09-23 Impact factor: 5.191
Authors: Nicolas Garbez; Litaty Mbatchi; Steven C Wallis; Laurent Muller; Jeffrey Lipman; Jason A Roberts; Jean-Yves Lefrant; Claire Roger Journal: Antimicrob Agents Chemother Date: 2021-06-17 Impact factor: 5.191
Authors: Lisa C Martial; Rob Ter Heine; Jeroen A Schouten; Nicole G Hunfeld; Henk J van Leeuwen; Paul E Verweij; Dylan W de Lange; Peter Pickkers; Roger J Brüggemann Journal: Clin Pharmacokinet Date: 2017-10 Impact factor: 6.447
Authors: Roeland E Wasmann; Eline W Muilwijk; David M Burger; Paul E Verweij; Catherijne A Knibbe; Roger J Brüggemann Journal: Clin Pharmacokinet Date: 2018-03 Impact factor: 6.447
Authors: Emilio Maseda; Santiago Grau; Sonia Luque; Maria-Pilar Castillo-Mafla; Alejandro Suárez-de-la-Rica; Ana Montero-Feijoo; Patricia Salgado; Maria-Jose Gimenez; Carlos A García-Bernedo; Fernando Gilsanz; Jason A Roberts Journal: Crit Care Date: 2018-04-15 Impact factor: 9.097
Authors: Kevin M Watt; Michael Cohen-Wolkowiez; Duane C Williams; Desiree K Bonadonna; Ira M Cheifetz; Dhiren Thakker; Daniel K Benjamin; Kim L R Brouwer Journal: J Extra Corpor Technol Date: 2017-09