60 - Evaluation of Outcomes Associated with Intermittent Versus Extended Infusion of Piperacillin/tazobactam in Acutely Ill Veterans.

Background: Antibiotic dosing optimization is a key principle of antimicrobial stewardship. This study evaluated the impact of an extended infusion piperacillin/tazobactam dosing protocol on clinical outcomes in acutely ill veterans treated for infections at VA San Diego.

Methods: This retrospective cohort study looked at veterans admitted to the medical-surgical unit who were treated with piperacillin/tazobactam for at least 48 hours. The control group included patients who received treatment between 12/14/2017 to 7/22/2018, and the “protocol” or after protocol implementation group included patients who received treatment between 7/23/2018 to 2/28/2019. Excluded from the study were veterans with microbiological cultures showing intermediate sensitivity or resistance to piperacillin/tazobactam, those who experienced interruption in therapy, or those who required dialysis. Primary clinical outcomes included in-hospital mortality rate, 30-day mortality rate, hospital length of stay (LOS), and 30-day readmission rates. Rates of adverse effects such as elevated liver enzymes, thrombocytopenia, acute kidney impairment (AKI), and Clostridium difficile infection were also collected. χ², Fisher’s exact, and Mann-Whitney U tests were used for statistical analysis.

Results: 260 veterans were included in the final analysis: 96% male, mean age 65 years, mean BMI 29, 84 met SIRS criteria for sepsis, and 55% received at least 48 hours of concomitant vancomycin. Groups had similar outcomes for median LOS, in-hospital mortality, and 30-day mortality. The incidence of AKI was significantly lower in the protocol group (39.2% vs. 56.9%, p=0.004), in veterans on concomitant vancomycin (42.3% vs. 63.2%, p=0.011), and in veterans with obesity (36.4% vs. 70.8%, p=0.001). Rates of liver enzyme elevation, thrombocytopenia, and C. difficile infection were lower in the protocol group though these were not significant.

Conclusion: There was a significantly lower rate of AKI with EI dosing which supports enhanced patient safety. This may be the preferred method of administration for obese patients and/or those receiving vancomycin concurrently. This is the first study to demonstrate that EI piperacillin/tazobactam dosing significantly reduces rates of AKI in patients on concomitant vancomycin.