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

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.

• Authors: 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, DALI Study Group
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 71 Issue 1 Pg. 196-207 (Jan 2016) ISSN: 1460-2091 [Electronic] England
• PMID: 26433783 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: [email protected].

Chemical References

• Anti-Bacterial Agents
• Thienamycins
• Piperacillin, Tazobactam Drug Combination
• Penicillanic Acid
• Meropenem
• Piperacillin

Topics

• Aged
• Anti-Bacterial Agents (administration & dosage, pharmacokinetics)
• Blood Chemical Analysis
• Critical Illness
• Female
• Humans
• Infusions, Intravenous
• Intensive Care Units
• Male
• Meropenem
• Microbial Sensitivity Tests
• Middle Aged
• Penicillanic Acid (administration & dosage, analogs & derivatives, pharmacokinetics)
• Piperacillin (administration & dosage, pharmacokinetics)
• Piperacillin, Tazobactam Drug Combination
• Prospective Studies
• Thienamycins (administration & dosage, pharmacokinetics)
• Treatment Outcome