Time above the MIC of Piperacillin-Tazobactam as a Predictor of Outcome in Pseudomonas aeruginosa Bacteremia

Abstract

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 %fT>MIC target 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>MIC of 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>MIC of >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 piperacillin-tazobactam with the aim of achieving a pharmacodynamic target %fT>MIC of at least 60% in these patients.

Effect of therapeutic drug monitoring-based dose optimization of piperacillin/tazobactam on sepsis-related organ dysfunction in patients with sepsis: a randomized controlled trial

“…Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection [1,2]. Emerging evidence suggests that in patients with sepsis, insufficient antibiotic exposure, defined as failure to meet the pharmacokinetic/pharmacodynamic (PK/PD) target to kill or inhibit the growth of a pathogen, is associated with worse clinical outcomes [3][4][5]. Previous studies demonstrated that up to 50% of critically ill patients receiving a β-lactam antibiotic with regimens based on the manufacturers' recommendations fail to reach the target [3,6].…”

The higher the better? Defining the optimal beta-lactam target for critically ill patients to reach infection resolution and improve outcome

“…Our new approach was forming an outcome group that the effect of antibiotic therapy is not masked by other measures and influences. A similar approach was recently performed by Tannous et al to predict the outcome of patients infected with Pseudomonas aeruginosa and treated with piperacillin-tazobactam [ 37 ].…”

A guide to therapeutic drug monitoring of β‐lactam antibiotics

“…[OR] 7.74, 95% confidence interval [CI] 1.31-45.2). 25 Compared with in vivo murine infection models, slightly higher fT>MIC exposures have been reported to be required to achieve clinical end points for carbapenems during patient studies. Li et al 26 identified meropenem fT>MIC of 54% was associated with microbiological eradication during the regulatory studies for lower respiratory tract infections.…”

“…In 79 patients treated with piperacillin‐tazobactam for P . aeruginosa bacteremia, >60.88% f T>MIC was associated with improved survival (odds ratio [OR] 7.74, 95% confidence interval [CI] 1.31–45.2) 25 …”