Time above the MIC of Piperacillin-tazobactam as a predictor of outcome in pseudomonas aeruginosa bacteremia

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.