Extended infusion versus intermittent infusion of Piperacillin/ tazobactam: altering current methods to optimize future outcome

ABSTRACT

Due to worldwide bacterial resistance, researchers and clinicians were required to optimize existing antimicrobials by influencing the pharmacokinetics and pharmacodynamics (PK/PD) features. Piperacillin/tazobactam (PIP/TZB) is one of the most frequently empirical antibiotics prescribed globally. The aim of the review was to evaluate the use of an extended infusion (EI) versus an intermittent infusion (II) of PIP/TZB in hospital settings in terms of patient safety and efficacy. Several PK/PD studies assessed the use of an extended infusion of PIP/TZB to reach different minimum inhibitory concentration (MIC) levels for many microorganisms including Pseudomonas aeruginosa. One of the main parameters to define the size of the effect of PIP/TZB to various microorganisms is the percentage of time the free drug concentration above MIC (%fT > MIC). Many studies have compared extended infusion (EI) versus intermittent infusion (II) in terms of mortality rate, clinical cure or efficacy, length of stay whether in an intensive care unit (ICU) or hospital, duration of therapy, and cost. The clinical data reviewed in this article include PK/PD studies, prospective trials, systematic reviews, and meta-analysis. The review emphasized the role of an extended infusion in a population with altered pharmacokinetics including patients on continuous renal replacement therapy (CRRT), critically ill patients with augmented renal clearance, and patients with cystic fibrosis. Our review reports a positive trend when using an extended infusion of PIP/TZB which encourages the adoption and implementation of the extended infusion to achieve positive patient outcomes. Nevertheless, more studies are required to attain generalizable and reliable data to determine whether an extended infusion improves patient outcomes. (AU)