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J Antimicrob Chemother. 2016 Jan;71(1):196-207. doi: 10.1093/jac/dkv288. Epub 2015 Oct 3.

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.

Collaborators (159)

Roberts JA, Lipman J, Starr T, Wallis SC, Paul S, Ribas AM, De Waele JJ, De Crop L, Spapen H, Wauters J, Dugernier T, Jorens P, Dapper I, De Backer D, Taccone FS, Rello J, Ruano L, Afonso E, Alvarez-Lerma F, Gracia-Arnillas MP, Fernández F, Feijoo N, Bardolet N, Rovira A, Garro P, Colon D, Castillo C, Fernado J, Lopez MJ, Fernandez JL, Arribas AM, Teja JL, Ots E, Montejo JC, Catalan M, Prieto I, Gonzalo G, Galvan B, Blasco MA, Meyer E, Del Nogal F, Vidaur L, Sebastian R, Garde PM, Del Mar Martin Velasco M, Crespo RZ, Esperatti M, Torres A, Montravers P, Baldesi O, Dupont H, Mahjoub Y, Lasocki S, Constantin JM, Payen JF, Martin C, Albanese J, Malledant Y, Pottecher J, Lefrant JY, Jaber S, Joannes-Boyau O, Orban C, Ostermann M, McKenzie C, Berry W, Smith J, Lei K, Rubulotta F, Gordon A, Brett S, Stotz M, Templeton M, Rhodes A, Ebm C, Moran C, Kaukonen KM, Pettilä V, Dimopoulos G, Koulenti D, Xristodoulou A, Theodorou V, Kouliatsis G, Sertaridou E, Anthopoulos G, Choutas G, Rantis T, Karatzas S, Balla M, Papanikolaou M, Myrianthefs P, Gavala A, Fildisis G, Koutsoukou A, Kyriakopoulou M, Petrochilou K, Kompoti M, Michalia M, Clouva-Molyvdas FM, Gkiokas G, Nikolakopoulos F, Psychogiou V, Malliotakis P, Akoumianaki E, Lilitsis E, Koulouras V, Nakos G, Kalogirou M, Komnos A, Zafeiridis T, Chaintoutis C, Arvaniti K, Matamis D, Chaintoutis C, Kydona C, Gritsi-Gerogianni N, Giasnetsova T, Giannakou M, Soultati I, Chytas I, Antoniadou E, Antipa E, Lathyris D, Koukoubani T, Paraforou T, Spiropoulou K, Bekos V, Spring A, Kalatzi T, Nikolaou H, Laskou M, Strouvalis I, Aloizos S, Kapogiannis S, Soldatou O, Bassetti M, Adembri C, Villa G, Giarratano A, Raineri SM, Cortegiani A, Montalto F, Strano MT, Ranieri VM, Sandroni C, De Pascale G, Molin A, Pelosi P, Montagnani L, Urbino R, Mastromauro I, De Rosa FG, Ranieri VM, Cardoso T, Afonso S, Gonçalves-Pereira J, Baptista JP, Akova M, Özveren A.

Author information

1
Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia.
2
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.
3
Department of Infectious Diseases, School of Medicine, Hacettepe University, Ankara, Turkey.
4
Infectious Diseases Division, Azienda Ospedaliera Universitaria Santa Maria della Misericordia, Udine, Italy.
5
Department of Critical Care Medicine, Ghent University Hospital, Ghent, Belgium.
6
Department of Critical Care, Attikon University Hospital, Athens, Greece.
7
Department of Anesthesiology and Intensive Care Medicine, Helsinki University Central Hospital, Helsinki, Finland.
8
Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia Department of Critical Care, Attikon University Hospital, Athens, Greece.
9
Anesthésie réanimation, Hospital Nord, Marseille, France AzuRea Group, Paris, France.
10
Département d'Anesthésie Réanimation, Centre Hospitalier Universitaire Bichat-Claude Bernard, AP-HP, Université Paris VII, Paris, France.
11
CIBERES, Vall d'Hebron Institut of Research, Universitat Autonoma de Barcelona, Barcelona, Spain.
12
St George's Healthcare NHS Trust and Department of Intensive Care Medicine, St George's University of London, London, UK.
13
Departments of Intensive Care Medicine and Pharmacy, Royal Brisbane and Women's Hospital, Brisbane, Australia.
14
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.

Abstract

OBJECTIVES:

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.

PMID:
26433783
DOI:
10.1093/jac/dkv288
[Indexed for MEDLINE]

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