• Marta Ulldemolins, Ignacio Martín-Loeches, Mireia Llauradó-Serra, Javier Fernández, Sergi Vaquer, Alejandro Rodríguez, Caridad Pontes, Gonzalo Calvo, Antoni Torres, and Dolors Soy.
• Fundació Privada Clínic per la Recerca Biomèdica, Barcelona, Spain Critical Care Department, Sabadell Hospital, University Institute Parc Taulí - Universitat Autònoma de Barcelona (UAB), Sabadell, Spain Universitat de Barcelona (UB), Barcelona, Spain marta.ulldemolins@gmail.com.
• J. Antimicrob. Chemother. 2016 Jun 1; 71 (6): 1651-9.

ObjectivesThis multicentre study aimed to describe the pharmacokinetics (PK) of piperacillin in critically ill patients with multiple organ dysfunction syndrome (MODS) receiving continuous venovenous haemodiafiltration (CVVHDF), to identify the sources of PK variability and evaluate different dosing regimens to develop recommendations based on clinical parameters.Patients And MethodsNineteen patients with MODS and CVVHDF receiving piperacillin/tazobactam were enrolled from three tertiary hospitals (95 plasma samples). Population PK modelling and Monte Carlo simulations were performed using NONMEM v7.3(®).ResultsPatients' median age was 70 years (range 39-82), median weight was 80 kg (45-129), median APACHE II score at admission was 21 (13-33) and median SOFA score on the day of study was 11 (8-21). The final population PK model was characterized by CL (L/h) = 6.11 * [weight (kg)/80](1.39) * CLMEMB. If membrane = 1.5 m(2) AN69ST, CLMEMB = 1; if membrane = 0.9 m(2) AN69, CLMEMB = 0.51. Monte Carlo simulations showed that: (i) to maintain unbound piperacillin concentrations above the MIC for the bacteria for 100% of dosing interval T (100%fuT>MIC), patients receiving CVVHDF with 1.5 m(2) AN69ST membranes required doses of 4000 mg q8h for the treatment of bacteria with a susceptibility to piperacillin close to the clinical breakpoint (MIC = 8-16 mg/L) (2000 mg q8h was sufficient for patients with CVVHDF using 0.9 m(2) AN69 membranes); and (ii) for the treatment of bacteria with high susceptibility to piperacillin (MIC <4 mg/L) or for the attainment of a more traditional pharmacodynamic target (50%fuT>MIC), 2000 mg q8h sufficed regardless of type of membrane and body weight.ConclusionsOur results suggest that type of membrane and body weight should be considered for piperacillin dose titration in critically ill patients with MODS and CVVHDF requirement.© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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