Tissue Penetration of Antibiotics in CriTically Ill Children

NCT07822243 | Recruiting FDA Drug

• 1 other identifier: BC-09534
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical study evaluates the extent to which three commonly administered beta-lactam antibiotics (piperacillin-tazobactam, meropenem, and amoxicillin-clavulanic acid) penetrate tissue in critically ill pediatric patients. The primary objectives of this study are to:

• Determine whether tissue penetration of beta-lactam antibiotics is impaired in critically ill pediatric patients during initial dosing and steady-state conditions.
• Evaluate whether antibiotic concentrations within interstitial tissue fluid achieve defined pharmacokinetic and pharmacodynamic targets.
• Assess the impact of patient demographics and clinical characteristics on antibiotic disposition in muscle tissue. Investigators will measure unbound antibiotic concentrations in tissue fluid using microdialysis, a technique involving the placement of a microdialysis catheter into the muscle tissue. Participating patients will undergo the following procedures:
• Insertion of a flexible microdialysis catheter into the vastus lateralis (thigh) muscle under continuous sedation.
• Administration of the prescribed antibiotic therapy in accordance with standard medical care.
• Collection of microdialysate and blood samples across specified dosing intervals to quantify tissue and plasma drug concentrations.

Conditions

Critical Illness; Pediatric Critical Illness

Keywords

Microdialysis; Antibiotics; Beta-lactams; Pharmacokinetics; Pediatric Intensive Care; Tissue Penetration; Meropenem; Piperacillin; Tazobactam; Amoxicillin; Clavulanic Acid; Tissue Pharmacokinetics; Pediatrics

Outcome Measures

Primary Outcomes (1)

• Tissue-to-plasma AUC ratio of beta-lactam antibiotics

  Ratio of the area under the concentration-time curve (AUC) of unbound beta-lactam antibiotic (piperacillin-tazobactam, meropenem, or amoxicillin-clavulanic acid) in skeletal muscle interstitial fluid (measured via microdialysis) to the AUC of total/unbound antibiotic in plasma. This evaluates the extent of tissue penetration.

  Up to 48 hours (measured over two separate dosing intervals)

Secondary Outcomes (1)

• Pharmacokinetic/pharmacodynamic (PK/PD) target attainment in plasma and tissue

  Up to 48 hours (across sampled dosing intervals)

Study Arms (1)

Critically Ill Pediatric Cohort

Critically ill pediatric patients (N=60 total) admitted to the Pediatric Intensive Care Unit (PICU) with continuous analgosedation who are prescribed routine intravenous therapy with one of three beta-lactam antibiotics (piperacillin-tazobactam, meropenem, or amoxicillin-clavulanic acid) as part of standard medical care. All participants undergo skeletal muscle microdialysis and paired blood sampling.

Other: Pharmacokinetic sampling (Microdialysis and blood sampling)

Interventions

Pharmacokinetic sampling (Microdialysis and blood sampling) OTHER

Intervention Description: Insertion of a 63 Microdialysis Catheter (M Dialysis AB; 20 kDa cutoff, 10 mm membrane) into the vastus lateralis muscle to measure unbound interstitial fluid antibiotic concentrations (calibrated using retrodialysis and an internal standard), combined with paired blood sampling via existing arterial/venous access to determine total and unbound plasma concentrations.

Critically Ill Pediatric Cohort

Eligibility Criteria

• Age: 1 Month - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

The study population consists of critically ill pediatric patients aged 1 month to 15 years admitted to the Pediatric Intensive Care Unit (PICU) of Ghent University Hospital who are receiving intravenous therapy with piperacillin-tazobactam, meropenem, or amoxicillin-clavulanic acid for known or suspected severe infection/sepsis. All included patients are under continuous analgosedation and mechanical ventilation at the time of microdialysis catheter placement and have established intra-arterial or intravenous access for routine blood sampling.

You may qualify if:

• Patient admitted to the Pediatric Intensive Care Unit (PICU).
• Age: 1 month to 15 years.
• Receiving intravenous antibiotic treatment with piperacillin-tazobactam, meropenem, or amoxicillin-clavulanic acid.
• Receiving continuous analgosedation (required for microdialysis catheter insertion; if analgosedation is stopped after insertion, the catheter may remain in place).
• Intra-arterial (preferred) or intravenous access available for blood sampling.

You may not qualify if:

• Presence of coagulopathy and/or thrombocytopenia:
• Platelet count \< 50,000/µL
• International Normalized Ratio (INR) \> 1.5
• Activated partial thromboplastin time (aPTT) \> 1.5 x upper limit of normal value (age-specific thresholds: \> 50 sec for 30-90 days; \> 42 sec for 90-180 days; \> 38 sec for \> 180 days)
• Personal or family history of excessive bleeding.
• Current treatment with coumarin derivative anticoagulants.
• Known hypersensitivity to beta-lactam antibiotics.
• Pregnancy.
• Absence of parental (or legal guardian) informed consent.
• Absence of suitable catheter for blood sampling.

Sponsors & Collaborators

• University Hospital, Ghent: lead

Study Sites (1)

Ghent University Hospital

Ghent, 9000, Belgium

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma and microdialysate samples collected during the study will be retained for bio-analysis: * Microdialysate samples: Dialysate collected at specified intervals from the microdialysis catheter inserted in the vastus lateralis muscle to quantify unbound interstitial antibiotic concentrations. * Plasma samples: Blood drawn concurrently via existing arterial or venous access to measure total antibiotic plasma levels and determine the protein-bound fraction via ultrafiltration.

MeSH Terms

Conditions

Critical Illness

Interventions

Microdialysis; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dialysis; Chemistry Techniques, Analytical; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative

Study Officials

• Pieter De Cock, Prof.

  University Hospital, Ghent

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pieter De Cock, Prof.

CONTACT

+32 9 332 29 69; pieter.decock@uzgent.be

Anca Amza

CONTACT

+ 32 9 332 18 83; anca.amza@uzgent.be

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2026
• First Posted: September 16, 2026
• Study Start: October 1, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: September 16, 2026

Record last verified: 2026-09

Locations

BE (1)