Piperacillin Pharmacokinetics in ICU Patients
Information source: University of Aarhus
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Sepsis; Septic Shock
Phase: N/A
Status: Recruiting
Sponsored by: Aarhus University Hospital Official(s) and/or principal investigator(s): Jakob Gjedsted, MD, PhD, Principal Investigator, Affiliation: Aarhus University Hospital, Department of Anesthesia and Intensive Care Medicine
Overall contact: Kristina Öbrink-Hansen, MD, Phone: +45 78452845, Email: krisoebr@rm.dk
Summary
Antibiotic dosing in critically ill patients poses a challenge for clinicians due to the
pharmacokinetic changes seen in this population. Piperacillin/tazobactam is often used for
empirical treatment, and initial appropriate dosing is crucial for reducing mortality.
Patients in the Intensive Care Unit (ICU), treated with piperacillin/tazobactam, had their
plasma concentration of piperacillin determined 1-3 times weekly. Patients received
piperacillin as intermittent bolus infusion 3 times daily or as continuous infusion (this
was up to the treating physician). Time above the minimal inhibitory concentration (T>MIC)
estimated for each patient was evaluated against clinical breakpoint MIC for Pseudomonas
aeruginosa (16 mg/L). Pharmacokinetic-pharmacodynamic (PK-PD) targets evaluated were 100% f
T>MIC (free piperacillin concentration maintained above the MIC throughout the dosing
interval) and 50% fT>4xMIC (free piperacillin concentration maintained at a level fourfold
the MIC for at least 50% of the dosing interval).
Clinical Details
Official title: Piperacillin Pharmacokinetics in Intensive Care Unit Patients Following Standard Treatment With Intermittent and Continuous Infusion
Study design: Observational Model: Case-Only, Time Perspective: Prospective
Primary outcome: Blood-plasma concentration of Piperacillin
Secondary outcome: Percentage of time above the minimal inhibitory concentration (T>MIC)
Detailed description:
Early appropriate antimicrobial therapy is of utmost importance for reducing mortality in
critically ill patients with sepsis and septic shock. Pathophysiological changes associated
with the septic process, such as changes in volume of distribution (Vd), drug clearance
(CL), decrease in plasma-protein concentration and organ dysfunction, lead to
pharmacokinetic (PK) changes that may alter the efficacy of the antimicrobial given. As a
consequence, antibiotic plasma concentrations are variable and hard to predict in these
patients, which makes optimal antibiotic exposure a challenge, especially in the early phase
of treatment.
Piperacillin/tazobactam is a β-lactam - β-lactamase inhibitor combination frequently used
for empirical treatment in the critically ill. It is a time-dependent antibiotic where
antibacterial activity is related to the time for which the free, unbound concentration of
the drug is maintained above the minimal inhibitory concentration (f T>MIC). Maximizing f
T>MIC both increases the therapeutic impact and reduces the risk of drug resistance
development. Because of the PK changes seen in the critically ill, standard dosing of
antimicrobials may result in subtherapeutic plasma-concentrations and it has been suggested
that current empiric dosing recommendations for Intensive Care Unit (ICU) patients are
inadequate and needs to be reconsidered.
Piperacillin/tazobactam is generally administered either as 4g/0. 5g every 8 hour (h) or as
12g given continuously over 24 hours. The aim of this study is to determine if this dosing
results in therapeutic plasma concentrations in septic patients. Patients treated with
piperacillin/tazobactam given as intermittent bolus infusion had piperacillin plasma
concentrations determined once a week. Patients treated with piperacillin/tazobactam given
as continuous infusion had piperacillin plasma concentrations determined three times a week.
Time above the minimal inhibitory concentration (T>MIC) estimated for each patient was
evaluated against clinical breakpoint MIC for Pseudomonas aeruginosa (16 mg/L).
Pharmacokinetic-pharmacodynamic (PK-PD) targets evaluated were 100% f T>MIC (free
piperacillin concentration maintained above the MIC throughout the dosing interval) and 50%
fT>4xMIC (free piperacillin concentration maintained at a level fourfold the MIC for at
least 50% of the dosing interval).
The unbound piperacillin plasma concentrations were determined using ultra high performance
liquid chromatography (UPLC). There was no intervention in the study.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Sepsis or septic shock
- Treatment with piperacillin/tazobactam
Exclusion Criteria:
- Age under 18 years
- Renal replacement therapy
Locations and Contacts
Kristina Öbrink-Hansen, MD, Phone: +45 78452845, Email: krisoebr@rm.dk
Aarhus Univbersity Hospital, Department of Anesthesia and Intensive Care Medicine, Aarhus N 8200, Denmark; Recruiting Jakob Gjedsted, MD, PhD, Phone: +45 78451030, Email: jakob.gjedsted@auh.rm.dk Kristina Öbrink-Hansen, MD, Phone: +45 78452845, Email: krobrink@gmail.com
Additional Information
Starting date: June 2015
Last updated: June 17, 2015
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