title: Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort.
abstract: OBJECTIVE
  We utilized the database of the Defining Antibiotic Levels in Intensive care unit patients (DALI) study to statistically compare the pharmacokinetic/pharmacodynamic and clinical outcomes between prolonged-infusion and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in critically ill patients using inclusion criteria similar to those used in previous prospective studies.
  
  
  METHODS
  This was a post hoc analysis of a prospective, multicentre pharmacokinetic point-prevalence study (DALI), which recruited a large cohort of critically ill patients from 68 ICUs across 10 countries.
  
  
  RESULTS
  Of the 211 patients receiving piperacillin/tazobactam and meropenem in the DALI study, 182 met inclusion criteria. Overall, 89.0% (162/182) of patients achieved the most conservative target of 50% fT>MIC (time over which unbound or free drug concentration remains above the MIC). Decreasing creatinine clearance and the use of prolonged infusion significantly increased the PTA for most pharmacokinetic/pharmacodynamic targets. In the subgroup of patients who had respiratory infection, patients receiving β-lactams via prolonged infusion demonstrated significantly better 30 day survival when compared with intermittent-bolus patients [86.2% (25/29) versus 56.7% (17/30); P = 0.012]. Additionally, in patients with a SOFA score of ≥9, administration by prolonged infusion compared with intermittent-bolus dosing demonstrated significantly better clinical cure [73.3% (11/15) versus 35.0% (7/20); P = 0.035] and survival rates [73.3% (11/15) versus 25.0% (5/20); P = 0.025].
  
  
  CONCLUSIONS
  Analysis of this large dataset has provided additional data on the niche benefits of administration of piperacillin/tazobactam and meropenem by prolonged infusion in critically ill patients, particularly for patients with respiratory infections.
authors.affiliation: Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia.
authors.forename: Mohd H
authors.initials: MH
authors.lastname: Abdul-Aziz
authors.affiliation: Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia Departments of Intensive Care Medicine and Pharmacy, Royal Brisbane and Women's Hospital, Brisbane, Australia.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lipman
authors.affiliation: Department of Infectious Diseases, School of Medicine, Hacettepe University, Ankara, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Akova
authors.affiliation: Infectious Diseases Division, Azienda Ospedaliera Universitaria Santa Maria della Misericordia, Udine, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Bassetti
authors.affiliation: Department of Critical Care Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: De Waele
authors.affiliation: Department of Critical Care, Attikon University Hospital, Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Dimopoulos
authors.affiliation: Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia Departments of Intensive Care Medicine and Pharmacy, Royal Brisbane and Women's Hospital, Brisbane, Australia.
authors.forename: Joel
authors.initials: J
authors.lastname: Dulhunty
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Kirsi-Maija
authors.initials: KM
authors.lastname: Kaukonen
authors.affiliation: Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia Department of Critical Care, Attikon University Hospital, Athens, Greece.
authors.forename: Despoina
authors.initials: D
authors.lastname: Koulenti
authors.affiliation: Anesthésie réanimation, Hospital Nord, Marseille, France AzuRea Group, Paris, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Martin
authors.affiliation: Département d'Anesthésie Réanimation, Centre Hospitalier Universitaire Bichat-Claude Bernard, AP-HP, Université Paris VII, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Montravers
authors.affiliation: CIBERES, Vall d'Hebron Institut of Research, Universitat Autonoma de Barcelona, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Rello
authors.affiliation: St George's Healthcare NHS Trust and Department of Intensive Care Medicine, St George's University of London, London, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Rhodes
authors.affiliation: Departments of Intensive Care Medicine and Pharmacy, Royal Brisbane and Women's Hospital, Brisbane, Australia.
authors.forename: Therese
authors.initials: T
authors.lastname: Starr
authors.affiliation: Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Wallis
authors.affiliation: Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia Departments of Intensive Care Medicine and Pharmacy, Royal Brisbane and Women's Hospital, Brisbane, Australia j.roberts2@uq.edu.au.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001774:Blood Chemical Analysis; D016638:Critical Illness; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007362:Intensive Care Units; D008297:Male; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010878:Piperacillin / Q000008:administration & dosage / Q000493:pharmacokinetics; D000077725:Piperacillin, Tazobactam Drug Combination; D011446:Prospective Studies; D013845:Thienamycins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; D000077731:Meropenem; D010878:Piperacillin