Are Standard Dosing Regimens of Piperacillin-Tazobactam Suitable in Critically Ill Patients With Open Abdomen and Negative Pressure Wound Therapy? A Population Pharmacokinetic Study.

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT04915872

Acronym

PK-LAP

Enrollment

Registered

2021-06-07

Start date

2021-07-01

Completion date

2023-01-27

Last updated

2023-02-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Critical Illness, Laparotomy, Piperacillin, Tazobactam Drug Combination

Keywords

Open Abdomen, Negative Pressure Therapy, Antibiotics, Piperacillin - Tazobactam, Pharmacokinetics

Brief summary

For several years, open abdomen with temporary abdominal closure using Negative Pressure Therapy (OA/NPT) has become one of the leading strategies to treat or prevent intra-abdominal hypertension in critically ill surgical patients after a wide range of complex abdominal injuries and conditions. According to current practice, piperacillin-tazobactam (PTZ) is widely used as part of empirical combined antibiotic therapy to treat severe abdominal infections in the critically ill patients. On the other hand, little is known about the impact of OA/NPT on antibiotics pharmacokinetics and pharmacodynamics (PK/PD) and the optimal dosing regimens in this population remain unclear. As PTZ is a small hydrophilic molecule with a very low level of protein binding, invesitigators hypothesized that OA/NPT should lead to significant changes in volume of distribution (Vd) and/or drug clearance (CL The main objective of this study was to assess the incidence of underdosing and the pharmacokinetics of piperacillin in critically ill patients with OA/NPT. The secondary objective was to assess the appropriateness of recommended regimens for empirical minimum inhibitory concentration (MIC) coverage.

Interventions

PROCEDUREBlood sampling (T0, inclusion)

Blood sample (5 ml) at 30 minutes after the loading dose of 4g/0.5g over 30 minutes for therapeutic drug monitoring at peak concentration (Cmax)

PROCEDUREother samplings (T1)

\- T1 : Day of the first surgical revision, under PTZ administered by continuous infusion : Blood sample (5 ml) for therapeutic drug monitoring at steady state concentration (Css). Urinary sample and collection of urinary volume between T0 and T1 (Urinary Clearance) NPT fluid sample and collection of NPT volume between T0 and T1 (Peritoneal Clearance) Peritoneal sampling for therapeutic drug monitoring at the site of infection (CPt)

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Age ≥ 18 * Admitted in surgical ICU for a suspected length of stay \> 3 days * Receiving an antimicrobial therapy by PTZ * For an intra-abdominal infection * Under OA/NPT during antimicrobial therapy * With urinary and arterial catheters

Exclusion criteria

* Severe renal failure (CLCR \< 30 ml/min) without indication for continuous renal replacement therapy (CRRT) * Known allergy to PTZ * Patient's refusal for participation to the research * Patient unable to consent (dementia or severe psychiatric disorders, people under legal protection, people deprived of their liberty...) * Pregnancy or breast-feeding

Design outcomes

Primary

Measure	Time frame	Description
Rate of piperacillin	T1 (Day of the first surgical revision, up to 72 hours after inclusion)	The main outcome investigated in this study was the rate of piperacillin (PIP) underdosing, arbitrarily defined by at least one of three samples under 16 mg/L. This threshold represents the highest MIC for Pseudomonas as per the European Committee on Antimicrobial Susceptibility Testing (EUCAST).

Countries

France

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026