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

Abstract

<i>Pseudomonas aeruginosa</i> 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 <i>Pseudomonas aeruginosa</i> infections. The pharmacokinetic-pharmacodynamic index associated with <i>in vitro</i> maximal bacterial killing for piperacillin-tazobactam is the percentage of the time between doses at which the free fraction concentration remains above the MIC (%<i>fT</i> _>MIC). However, the precise %<i>fT</i> _>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 <i>Pseudomonas aeruginosa</i> bacteremia and the threshold of the piperacillin-tazobactam %<i>fT</i> _>MIC This retrospective study included all adult patients hospitalized over an 82-month period with <i>Pseudomonas aeruginosa</i> 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 %<i>fT</i> _>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 %<i>fT</i> _>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 %<i>fT</i> _>MIC of at least 60% in these patients.