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Time above the MIC of piperacillin-tazobactam as a predictor of outcome in pseudomonas aeruginosa bacteraemia.

Tannous, Elias; Lipman, Shelly; Tonna, Antonella; Hector, Emma; Hussein, Ziad; Stein, Michal; Reisfeld, Sharon


Elias Tannous

Shelly Lipman

Emma Hector

Ziad Hussein

Michal Stein

Sharon Reisfeld


All rights reserved. Pseudomonas aeruginosa bacteremia is an infection associated with a high mortality rate. Piperacillin-tazobactam is a β-lactam-β-lactamase inhibitor combination that is frequently used for the management of Pseudomonas aeruginosa infections. The pharmacokinetic-pharmacodynamic index associated with in vitro maximal bacterial killing for piperacillin-tazobactam is the percentage of the time between doses at which the free fraction concentration remains above the MIC (%fT>MIC). However, the precise %>MICtarget associated with improved clinical outcomes is unknown. The aim of this study was to investigate the correlation between the survival of patients with Pseudomonas aeruginosa bacteremia and the threshold of the piperacillin-tazobactam %fT>MIC. This retrospective study included all adult patients hospitalized over an 82-month period with Pseudomonas aeruginosa bacteremia and treated with piperacillin-tazobactam. Patients with a polymicrobial infection or those who died within 72 h of the time of collection of a sample for culture were excluded. The %fT>MICof piperacillin-tazobactam associated with in-hospital survival was derived using classification and regression tree analysis. After screening 270 patients, 78 were eligible for inclusion in the study; 18% died during hospitalization. Classification and regression tree analysis identified a %fT>MICof >60.68% to be associated with improved survival, and this remained statistically significant after controlling for clinical covariates (odds ratio=7.74, 95% confidence interval=1.32 to 45.2). In conclusion, the findings recommend dosing of piperacillintazobactam with the aim of achieving a pharmacodynamic target %fT>MICof at least 60% in these patients.


TANNOUS, E., LIPMAN, S., TONNA, A., HECTOR, E., HUSSEIN, Z., STEIN, M., and REISFELD, S. 2020. Time above the minimum inhibitory concentration of piperacillin/tazobactam as a predictor of outcome in Pseudomonas aeruginosa bacteraemia. Antimicrobial agents and chemotherapy [online], 64(8), article ID e02571-19. Available from:

Journal Article Type Article
Acceptance Date May 21, 2020
Online Publication Date Jun 1, 2020
Publication Date Jul 22, 2020
Deposit Date Jun 9, 2020
Publicly Available Date Dec 2, 2020
Journal Antimicrobial agents and chemotherapy
Print ISSN 0066-4804
Electronic ISSN 1098-6596
Publisher American Society for Microbiology
Peer Reviewed Peer Reviewed
Volume 64
Issue 8
Article Number e02571-19
Keywords Pseudomonas aeruginosa bacteraemia; Mortality; Infection; Piperacillin; Tazobactam; Bacteria Pharmacology; Infectious Diseases
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