title: Piperacillin population pharmacokinetics in critically ill patients with multiple organ dysfunction syndrome receiving continuous venovenous haemodiafiltration: effect of type of dialysis membrane on dosing requirements.
abstract: This 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.
  
  
  
  Nineteen 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(®).
  
  
  
  Patients' 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.
  
  
  
  Our 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.
authors: 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.
authors: Marta
authors: M
authors: Ulldemolins
authors: Critical Care Department, Sabadell Hospital, University Institute Parc Taulí - Universitat Autònoma de Barcelona (UAB), Sabadell, Spain Multidisciplinary Intensive Care Research Organization (MICRO), Critical Care Department, St James University Hospital, Trinity Centre for Health Sciences, Dublin, Ireland Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors: Ignacio
authors: I
authors: Martín-Loeches
authors: Nursing Department, Universitat Rovira i Virgili (URV), Tarragona, Spain Critical Care Department, Joan XXIII University Hospital, Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain.
authors: Mireia
authors: M
authors: Llauradó-Serra
authors: Universitat de Barcelona (UB), Barcelona, Spain Liver Department, Hospital Clínic de Barcelona, Barcelona, Spain Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), Madrid, Spain.
authors: Javier
authors: J
authors: Fernández
authors: Critical Care Department, Sabadell Hospital, University Institute Parc Taulí - Universitat Autònoma de Barcelona (UAB), Sabadell, Spain.
authors: Sergi
authors: S
authors: Vaquer
authors: Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain Critical Care Department, Joan XXIII University Hospital, Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Tarragona, Spain.
authors: Alejandro
authors: A
authors: Rodríguez
authors: Clinical Pharmacology Unit, Hospital de Sabadell, Institut Universitari Parc Taulí - Universitat Autònoma de Barcelona, Sabadell, Spain Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain.
authors: Caridad
authors: C
authors: Pontes
authors: Universitat de Barcelona (UB), Barcelona, Spain Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain Department of Clinical Pharmacology, Hospital Clínic de Barcelona, Barcelona, Spain.
authors: Gonzalo
authors: G
authors: Calvo
authors: Fundació Privada Clínic per la Recerca Biomèdica, Barcelona, Spain Universitat de Barcelona (UB), Barcelona, Spain Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain Respiratory Critical Care Unit, Pneumology Department, Institut Clínic del Tòrax, Hospital Clínic de Barcelona, Barcelona, Spain.
authors: Antoni
authors: A
authors: Torres
authors: Fundació Privada Clínic per la Recerca Biomèdica, Barcelona, Spain Universitat de Barcelona (UB), Barcelona, Spain Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain Pharmacy Department, Hospital Clínic de Barcelona, Barcelona, Spain.
authors: Dolors
authors: D
authors: Soy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001835:Body Weight; D002853:Chromatography, Liquid; D016638:Critical Illness; D005260:Female; D017583:Hemodiafiltration; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009102:Multiple Organ Failure; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010878:Piperacillin / Q000008:administration & dosage / Q000493:pharmacokinetics; D000077725:Piperacillin, Tazobactam Drug Combination; D010949:Plasma / Q000737:chemistry; D011446:Prospective Studies; D062606:Tertiary Care Centers; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D010878:Piperacillin