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 Abdulaziz,Jeffrey Lipman,M Akova,Matteo Bassetti,Jan J De Waele,George Dimopoulos,Joel M Dulhunty,Kirsimaija 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 De Crop,Herbert D Spapen,Joost Wauters, T Dugernier,Philippe G Jorens, Ilse Dapper,Daniel De Backer,Fabio Taccone, Laura Ruano,E Afonso, F Alvarezlerma, M P Graciaarnillas, F Fernandez,Neus Feijoo,Neus Bardolet,Assumpta Rovira,Pau Garro, Diana Colon,Carlos Castillo,Juan Fernado,Maria Jesus Lopez,J L Fernandez, Ana Maria Arribas, Jose Luis Teja, Elsa Ots,Juan Carlos Montejo, M Catalan, Isidro Prieto,Gloria Gonzalo,Beatriz Galvan,Miguel Angel Blasco,Estibaliz Meyer, Frutos Del Nogal,Loreto Vidaur, Rosa Sebastian, Pila Marco Garde, M Velasco,R Crespo,Mariano Esperatti,Antoni Torres,Olivier Baldesi,H Dupont, Y Mahjoub,Sigismond Lasocki, J M Constantin, J F Payen,Jacques Albanese,Yannick Malledant,Julien Pottecher,Jeanyves Lefrant,Samir Jaber,O Joannesboyau,Christophe Orban,Marlies Ostermann,Catherine A Mckenzie, Willaim Berry, J P Smith,Katie Lei,Francesca Rubulotta,Anthony C Gordon,Stephen J Brett,Martin Stotz,Maie Templeton, C Ebm, Carl Moran,Ville Pettila,Aglaia Xristodoulou,Vassiliki Theodorou,Georgios Kouliatsis,Eleni Sertaridou,Georgios Anthopoulos,George Choutas,Thanos Rantis,Stylianos Karatzas,Margarita Balla,Metaxia N Papanikolaou,Pavlos M Myrianthefs,Alexandra Gavala, Georgios Fildisis,Antonia Koutsoukou,Magdalini Kyriakopoulou,Kalomoira Petrochilou,Maria Kompoti,Martha Michalia,Fillismaria Clouvamolyvdas,Georgios Gkiokas,Fotios Nikolakopoulos,Vasiliki Psychogiou,Polychronis Malliotakis, E Akoumianaki, Emmanouil Lilitsis, V Koulouras,George Nakos,Mihalis Kalogirou,Apostolos Komnos,Tilemachos Zafeiridis, Christos Chaintoutis,Kostoula Arvaniti,Dimitrios Matamis, C Kydona, N Gritsigerogianni,Tatiana Giasnetsova, Maria Giannakou, I Soultati,Ilias Chytas,Eleni Antoniadou,Elli Antipa, D Lathyris, Triantafyllia Koukoubani, Theoniki Paraforou,Kyriaki Spiropoulou,Vasileios Bekos, Anna Spring,Theodora Kalatzi,Hara Nikolaou, Maria Laskou,Ioannis Strouvalis,Stavros Aloizos,Spyridon Kapogiannis,Ourania Soldatou,Chiara Adembri,Gianluca Villa,Antonio Giarratano,Santi Maurizio Raineri,Andrea Cortegiani, Francesca Montalto, Maria Teresa Strano,V Marco Ranieri,Claudio Sandroni, G Pascale, Alexandre Molin,Paolo Pelosi, Luca Montagnani,Rosario Urbino, Ilaria Mastromauro,Francesco G De Rosa,Teresa Cardoso, Susana Afonso,Joao Goncalvespereira,J P Baptista,Arife Ozveren

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY（2016）

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摘要

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 beta-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.

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