Piperacillin Pharmacokinetics in ICU Patients

NCT ID: NCT02478073

Last Updated: 2015-06-23

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 50 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-06-30
• Study Completion Date: 2016-05-31

Brief 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).

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.

Conditions

Sepsis; Septic Shock

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• Sepsis or septic shock
• Treatment with piperacillin/tazobactam

Exclusion Criteria

• Age under 18 years
• Renal replacement therapy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aarhus University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jakob Gjedsted, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Aarhus University Hospital, Department of Anesthesia and Intensive Care Medicine

Locations

Aarhus Univbersity Hospital, Department of Anesthesia and Intensive Care Medicine

Aarhus N, , Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Kristina Öbrink-Hansen, MD

Role: CONTACT

krisoebr@rm.dk

+45 78452845

Jakob Gjedsted, MD, PhD

Role: CONTACT

jakob.gjedsted@auh.rm.dk

+45 7845 1030

Facility Contacts

Jakob Gjedsted, MD, PhD

Role: primary

jakob.gjedsted@auh.rm.dk

+45 78451030

Kristina Öbrink-Hansen, MD

Role: backup

krobrink@gmail.com

+45 78452845

Other Identifiers

AB-ICU

Identifier Type: -

Identifier Source: org_study_id