TY - JOUR
T1 - 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
AU - on behalf of the DALI Study Group
AU - Abdul-Aziz, Mohd H.
AU - Lipman, Jeffrey
AU - Akova, Murat
AU - Bassetti, Matteo
AU - De Waele, Jan J.
AU - Dimopoulos, George
AU - Dulhunty, Joel
AU - Kaukonen, Kirsi Maija
AU - Koulenti, Despoina
AU - Martin, Claude
AU - Montravers, Philippe
AU - Rello, Jordi
AU - Rhodes, Andrew
AU - Starr, Therese
AU - Wallis, Steven C.
AU - Roberts, Jason A.
AU - Paul, Sanjoy
AU - Ribas, Antonio Margarit
AU - De Crop, Luc D.
AU - Spapen, Herbert
AU - Wauters, Joost
AU - Dugernier, Thierry
AU - Jorens, Philippe
AU - Dapper, Ilse
AU - De Backer, Daniel D.
AU - Taccone, Fabio S.
AU - Ruano, Laura
AU - Afonso, Elsa
AU - Alvarez-Lerma, Francisco
AU - Gracia-Arnillas, Maria Pilar
AU - Fernández, Francisco
AU - Feijoo, Neus
AU - Bardolet, Neus
AU - Rovira, Assumpta
AU - Garro, Pau
AU - Colon, Diana
AU - Castillo, Carlos
AU - Fernado, Juan
AU - Lopez, Maria Jesus
AU - Fernandez, Jose Luis
AU - Arribas, Ana Maria
AU - Teja, Jose Luis
AU - Ots, Elsa
AU - Montejo, Juan Carlos
AU - Catalan, Mercedes
AU - Prieto, Isidro
AU - Gonzalo, Gloria
AU - Galvan, Beatriz
AU - Blasco, Miguel Angel
AU - Payen, Jean François
N1 - Publisher Copyright:
© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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.
AB - 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.
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U2 - 10.1093/jac/dkv288
DO - 10.1093/jac/dkv288
M3 - Article
C2 - 26433783
AN - SCOPUS:84960122710
SN - 0305-7453
VL - 71
SP - 196
EP - 207
JO - Journal of Antimicrobial Chemotherapy
JF - Journal of Antimicrobial Chemotherapy
IS - 1
ER -