Assessment of the Optimal Dosing of Piperacillin-tazobactam in Intensive Care Unit Patients: Extended Versus Continuous Infusion

Ghent University Hospital (UZ)

Status and phase: Completed; Phase 4

Conditions: Infectious Disease

Treatments: Drug: piperacillin extended infusion; Drug: piperacillin continuous infusion

Study type: Interventional

Funder types: Other

Identifiers

NCT01198925

2010/414

Details and patient eligibility

About

Piperacillin-tazobactam is an acylureido-penicillin-beta-lactamase inhibitor combination and is frequently used in the empirical treatment of hospital-acquired infections because of its antipseudomonal activity. Similar to other beta-lactam antibiotics, piperacillin-tazobactam exhibits time-dependent killing and the T > MIC appears to be the best outcome predictor. Because a majority of infections are treated empirically, it is necessary to achieve a T > MIC equal to 50% of the dosing interval (50% T > MIC) against the most likely pathogens, including those with only moderate susceptibility The aim of this study is to compare the same dose of piperacillin/tazobactam administered by an extended infusion versus a continuous infusion. A pharmacokinetic study will be performed in patients treated by extended (loading dose 4 G/30 min followed by 4 X 4 G /3h) and continuous infusion (loading dose 4 G/30 min followed by 16G /24h).

A population pharmacokinetic analysis with Monte Carlo simulations will be used to determine 95% probability of target attainment (PTA95) versus MIC

Enrollment: 14 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult patients (> 18 years) admitted on the intensive care unit (surgical and medical surgery).
• Starting a treatment with piperacillin/tazobactam
• Signed informed consent
• Hematocrit >= 21%
• Available arterial line

Exclusion criteria

• age <18 or >75 years
• patient's weight <50 or >100 kg
• renal insufficiency (estimated clearance < 50 ML /MIN)
• haemodialysis
• WBC < 1000 103 µl
• estimated survival <5 days
• meningitis or other proven infections of the CNS
• IgE-mediated allergy to penicillins
• pregnancy
• patients having participated in another study <30 days before inclusion in the present study
• retrospectively, marked deterioration of the renal function during the study period
• retrospectively, treatment < 96 h

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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14 participants in 2 patient groups

extended infusion

Active Comparator group

Treatment:

Drug: piperacillin extended infusion

continuous infusion

Experimental group

Treatment:

Drug: piperacillin continuous infusion