Extended Infusion Piperacillin/Tazobactam Reduces Risk of Mortality, C Difficile Infections

Extended infusion piperacillin/tazobactam administered in a hospital setting could reduce the risk of mortality and other negative outcomes, even in non-critically ill patients.¹

A team, led by AJ Chan, Department of Pharmacy, Unity Health Toronto, compared the clinical, safety, and economic outcomes of patients given extended infusion with piperacillin/tazobactam with standard infusion and piperacillin/ tazobactam.

Previous research has shown that extended infusion piperacillin/tazobactam results in improved clinical outcomes compared to standard infusion treatment.

However, there remains a gap in knowledge comparing the 2 options for non-critically ill patients.

Gram-negative infections are associated with significant morbidity and mortality among hospitalized patients. The emergence of resistant organisms has outpaced the development of new antibiotics,” the authors wrote. “One way to optimize the use of current antimicrobials is to apply innovative pharmacokinetic/pharmacodynamic (PK/PD) dosing strategies to improve clinical outcomes.”

One potential treatment is piperacillin/tazobactam, which has shown time-dependent killing with a goal of time above minimum inhibitory concentration of 50-60% resulting in a bactericidal effect.

Prior to the investigators implemented hospital-wide extended infusion piperacillin/tazobactam therapy as of February 21, 2012.

In the retrospective cohort study, the investigators examined all adult patients who received extended infusion piperacillin/tazobactam 3.375 g intravenous q8h infusion over 4 hours (n = 2034) and standard infusion piperacillin/tazobactam (n = 1634) for at least 48 hours over the course of 3 years.

The investigators sought primary outcomes of the 14-day mortality. They also looked at various secondary outcomes, including length of hospital stay, nursing plus pharmacy cost, occurrence of clostridioides difficile infection, readmission within 30 days and change in P. aeruginosa minimum inhibitory concentration (MIC) distribution for the treatment.

The team used a logistic regression model to analyze both primary and secondary outcomes and examined length of stay using time to event analysis.

Overall, extended infusion was linked to lower odds of mortality (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.63-0.91), as well as lower odds of C difficile infections (OR, 0.59; 95% CI, 0.41-0.84) and an 8% lower cost (estimate 0.92, 95% CI 0.87-0.98) compared to the standard infusion.

The results also show the standard infusion group had more patients with P. aeruginosa isolates from blood and respiratory cultures, ICU status at the start of therapy and longer duration of treatment.

For the unadjusted outcomes, the extended infusion cohort had fewer patients who died within 14 days, shorter length of stay, lower incidence of C. difficile infection, lower nursing costs and total costs.

However, in the adjusted analysis, there was no difference found in length of stay or readmission within 30 days between the 2 treatment cohorts.

“Hospital-wide implementation of EI TZP was associated with lower odds of 14-day mortality and incidence of C. difficile infection with cost savings at our institution,” the authors wrote.