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

Mohd H. Abdul-Aziz, Jeffrey Lipman, Murat Akova, Matteo Bassetti, Jan J. De Waele, George Dimopoulos, Joel Dulhunty, Kirsi Maija Kaukonen, Despoina Koulenti, Claude Martin, Philippe Montravers, Jordi Rello, Andrew Rhodes, Therese Starr, Steven C. Wallis, Jason A. Roberts, Sanjoy Paul, Antonio Margarit Ribas, Luc D. De Crop, Herbert SpapenJoost Wauters, Thierry Dugernier, Philippe Jorens, Ilse Dapper, Daniel D. De Backer, Fabio S. Taccone, Laura Ruano, Elsa Afonso, Francisco Alvarez-Lerma, Maria Pilar Gracia-Arnillas, Francisco Fernández, Neus Feijoo, Neus Bardolet, Assumpta Rovira, Pau Garro, Diana Colon, Carlos Castillo, Juan Fernado, Maria Jesus Lopez, Jose Luis Fernandez, Ana Maria Arribas, Jose Luis Teja, Elsa Ots, Juan Carlos Montejo, Mercedes Catalan, Isidro Prieto, Gloria Gonzalo, Beatriz Galvan, Miguel Angel Blasco, Estibaliz Meyer, Frutos Del Nogal, Loreto Vidaur, Rosa Sebastian, Pila Marco Garde, Maria del Mar Martin Velasco, Rafael Zaragoza Crespo, Mariano Esperatti, Antoni Torres, Olivier Baldesi, Herve Dupont, Yazine Mahjoub, Sigismond Lasocki, Jean Michel Constantin, Jean François Payen, Jacques Albanese, Yannick Malledant, Julien Pottecher, Jean Yves Lefrant, Samir Jaber, Olivier Joannes-Boyau, Christophe Orban, Marlies Ostermann, Catherine McKenzie, Willaim Berry, John Smith, Katie Lei, Francesca Rubulotta, Anthony Gordon, Stephen Brett, Martin Stotz, Maie Templeton, Claudia Ebm, Carl Moran, Ville Pettilä, Aglaia Xristodoulou, Vassiliki Theodorou, Georgios Kouliatsis, Eleni Sertaridou, Georgios Anthopoulos, George Choutas, Thanos Rantis, Stylianos Karatzas, Margarita Balla, Metaxia Papanikolaou, Pavlos Myrianthefs, Alexandra Gavala, Georgios Fildisis, Antonia Koutsoukou, Magdalini Kyriakopoulou, Kalomoira Petrochilou

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Abstract

© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. 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.
Original languageEnglish
Pages (from-to)196-207
JournalJournal of Antimicrobial Chemotherapy
Volume71
Issue number1
DOIs
Publication statusPublished - 1 Jan 2016

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