Implementation of Extended-Infusion Piperacillin-Tazobactam Protocol

From the 2021 HVPAA National Conference

Michael Burns (Walter Reed National Military Medical Center), Andrew Weskamp, Minki Hong, Sinead Cooper, Berly Vincent, Zachary Johnston, Michael Kavanaugh


Piperacillin-tazobactam is a beta-lactam antibiotic commonly used for broad-spectrum coverage for patients presenting with sepsis. Beta-lactam antibiotics kill bacteria in a time-dependent manner, where a greater amount of time that the drug spends above the minimum inhibitory concentration (MIC) leads to greater bactericidal effect. Traditional dosing involves an intermittent infusion model, in which piperacillin-tazobactam is given every six hours over thirty minutes. Pharmacokinetic analysis has shown that this dosing pattern leads to poor overall time above MIC. Over the last fifteen years, an extended infusion dosing strategy, in which piperacillin-tazobactam is given every eight hours over four hours, has been increasingly implemented in hospitals. This has led to the Infectious Diseases Society of America (IDSA) to advocate for use of extended-infusion dosing over the standard dosing in their 2017 Antimicrobial Stewardship Guidelines.


Utilizing extended infusion piperacillin-tazobactam, we aim to reduce the average number of doses of piperacillin-tazobactam per treatment course of adult inpatients by 20% over a five-month period.


An interdisciplinary team consisting of physicians, nurses, and pharmacists was assembled. All physicians, inpatient nursing staff, and inpatient pharmacists were educated on extended infusion dosing protocol. This protocol involved an initial bolus dose of piperacillin-tazobactam over thirty minutes, followed four hours later by the extended infusion protocol of four-hour infusion every eight hours. On the go live date, existing piperacillin-tazobactam orders were deleted and replaced with new orders and an order set was created to facilitate proper use.

Our population for this project were patients age 18 or older admitted to our hospital between 7/1/2019 -11/30/2019 (pre-intervention) and 7/1/2020-11/30/2020 (post-intervention) who received at least one dose of piperacillin-tazobactam while inpatient. We excluded any individuals who received only a single dose of piperacillin-tazobactam while in the Emergency Department. A new treatment course was defined after more than 24 hours since the last dose of piperacillin-tazobactam was administered to account for patients with multiple admissions or multiple courses within one admission.


In the pre-intervention period, a total of 2556 doses over 231 treatment courses met the above parameters, for an average of 11.1 doses per treatment course. In the post-intervention period, a total of 1356 doses over 160 treatment courses were administered, for an average of 8.5 doses per treatment course.


Our project achieved our objective by effectively reducing the average number of doses of piperacillin-tazobactam per treatment course by 23%. Within the post-intervention period, this resulted in a decrease of 416 administered doses. Based on an average price of piperacillin-tazobactam of $15.24 per dose, this results to an approximate cost savings of $6,340 over this period, which extrapolates to over $15,000 over the course of a year.

Clinical Implication

This project demonstrated the importance of an interdisciplinary approach when implementing hospital-wide changes. Without buy-in from all services, projects of this caliber can fall flat. Through this effort, we were able demonstrate how to successfully implement a hospital-wide medication protocol to achieve standard of care practice, while additionally providing cost savings that can be re-invested elsewhere.

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