- Design
- Open-label randomised feasibility trial
- Population
- 45 adults with BMI ≥30 starting piperacillin-tazobactam
- Primary outcome
- Feasibility; exploratory 100% fT>MIC at 24 hours
- Effect
- 100% fT>MIC in 64.3% (prolonged) vs 55.6% (standard), P = 0.725
This open-label randomised feasibility trial enrolled 45 adults with a BMI of 30 or more starting piperacillin-tazobactam and assigned them to standard or prolonged infusions. A 24-hour blood sample measured piperacillin concentrations.
The trial met its recruitment targets, though sample collection fell just short. In an exploratory analysis, 64% of patients on prolonged infusions and 56% on standard infusions maintained free drug concentrations above the MIC for the whole dosing interval — a difference that was not statistically significant. Safety outcomes were similar.
Piperacillin kills in a time-dependent way, so the time the free drug stays above the MIC matters more than the peak. A larger volume of distribution in obesity can lower concentrations, which is the rationale for extended infusions. This trial was not designed to show a difference; it shows a larger one can be run.
- Consider prolonged or extended piperacillin-tazobactam infusions in patients with obesity where local protocols support them.
- Use therapeutic drug monitoring for beta-lactams where available in severe infection or extremes of weight.
- Check infusion compatibility and line access before switching to prolonged infusions.
- Treat this as feasibility data, not evidence of better clinical outcomes.
Why it matters
It opens the way to testing a simple dosing change in a group often under-dosed.
Don't overread it
A 45-patient feasibility trial does not show that prolonged infusions improve cure or survival.
The statistics, in plain English
The difference between 64% and 56% had a P value of 0.73, meaning it could easily be chance in a trial this small. Feasibility trials are not powered to compare outcomes.
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