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Published on: August 30, 2018
Effectiveness of piperacillin/tazobactam loading dose for extended infusion dosing among patients with Gram-negative
Savan Patel1,2, Sana Mohayya2, Arsheena Yassin2
1Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, NJ, USA.
Objective:
To examine the effect of a loading dose (LD) for extended infusion piperacillin/tazobactam on clinical outcomes.
Methods:
This single-centre, retrospective cohort study evaluated adult patients with Gram-negative bacteraemia who received extended infusion piperacillin/tazobactam for ≥48 hours between 2015 and 2022. In December 2019, the study institution developed a policy that automatically ordered a piperacillin/tazobactam LD whenever piperacillin/tazobactam was prescribed. The study compared patients who received piperacillin/tazobactam LD to those who did not. The primary endpoint was 30-day all-cause mortality. Key secondary endpoints included clinical cure, 14-day all-cause mortality, in-hospital all-cause mortality and microbiologic cure. Logistic regression modelling was performed to control for confounding variables.
Results:
A total of 151 patients were included in the analysis, with 84 patients in the LD group and 67 patients in the no LD group. Baseline characteristics were similar in both treatment groups, except for immunocompromised status, severity of illness and serum creatinine, with most mortality prognosticators in the LD group. In the bivariate analysis, 30-day mortality was 10.7% (9/84) in the LD group compared to 9.0% (6/67) in the no LD group (P = 0.72). This was consistent with the multivariable logistic regression model (adjusted OR, 0.71; 95% CI, 0.21-2.41).
Conclusions:
Overall, we observed no significant association between LD for extended infusion piperacillin/tazobactam and mortality, and no signal that use of LD was associated with more adverse events. We hypothesize a potential benefit of LD administration for severely ill patients, but larger adequately powered prospective cohorts or randomized trials are needed to examine this.
Insights
A loading dose (LD) of piperacillin/tazobactam did not significantly impact 30-day mortality in Gram-negative bacteraemia patients. Further research is needed to explore potential benefits in critically ill individuals.
Area of Science:
- Infectious Diseases
- Pharmacology
- Clinical Pharmacy
Background:
- Extended infusion piperacillin/tazobactam is used for Gram-negative bacteraemia.
- The role of a loading dose (LD) in this regimen is not well-established.
- Optimizing antibiotic dosing is crucial for patient outcomes.
Purpose of the Study:
- To evaluate the impact of a piperacillin/tazobactam loading dose (LD) on clinical outcomes in patients with Gram-negative bacteraemia.
- To compare mortality and cure rates between patients receiving extended infusion piperacillin/tazobactam with and without an LD.
Main Methods:
- Retrospective cohort study of 151 adult patients with Gram-negative bacteraemia receiving extended infusion piperacillin/tazobactam.
- Comparison of patients who received an LD versus those who did not, following a policy change in December 2019.
- Primary endpoint: 30-day all-cause mortality. Secondary endpoints included clinical, 14-day, in-hospital mortality, and microbiologic cure.
- Logistic regression was used to adjust for confounding variables.
Main Results:
- No significant difference in 30-day all-cause mortality between the LD group (10.7%) and the no LD group (9.0%) (P=0.72).
- Multivariable analysis showed no significant association between LD and 30-day mortality (adjusted OR, 0.71; 95% CI, 0.21-2.41).
- Baseline characteristics were similar, though the LD group had more immunocompromised patients and higher illness severity.
Conclusions:
- The study found no significant association between the use of a loading dose for extended infusion piperacillin/tazobactam and mortality or adverse events.
- A potential benefit of LD in severely ill patients is hypothesized.
- Larger prospective studies or randomized trials are required to confirm these findings.
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