Tissue Penetration of Antibiotics in CriTically Ill Children
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age1-15
SponsorUniversity Hospital, Ghent
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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).
Disqualifiers
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.
Trial 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.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Pharmacokinetic sampling (Microdialysis and blood sampling)
Other interventionIntervention 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.
Treatment groups
60 Participants
are divided into 1 treatment groupGroup A: Critically Ill Pediatric Cohort1 intervention
Trial outcomes
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.
Time frame
Up to 48 hours (measured over two separate dosing intervals)Secondary outcomes
1
Pharmacokinetic/pharmacodynamic (PK/PD) target attainment in plasma and tissue
Percentage of time during the dosing interval that unbound plasma and tissue antibiotic concentration remains above the Minimum Inhibitory Concentration (%fT\>MIC) of the target micro-organism in interstitial fluid.
Time frame
Up to 48 hours (across sampled dosing intervals)Sponsors and contacts
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Source ClinicalTrials.gov