Surgical Site Infection Study

Study Overview
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Brief Summary
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The purpose of this study is to investigate the pharmacokinetics of cefazolin using both plasma and microdialysate sampling methods in children with single ventricle physiology undergoing their second palliation procedure. This will provide data to determine if the current standard dosing regimen of cefazolin is adequate to achieve and maintain tissue concentrations greater than the minimum inhibitory concentrations (MIC) for common post-surgical pathogens that cause Surgical Site Infections (SSIs).

Detailed Description
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This study aims to sample interstitial fluid (IF) of infants undergoing superior cava-pulmonary anastomosis (either Glenn or Hemi-Fontan) cardiac surgical procedures who receive cefazolin as their surgical prophylactic antibiotic. Cefazolin concentrations will then be determined in both microdialysate and plasma samples and used to define the pharmacokinetics of cefazolin at the tissue level and compare that to plasma pharmacokinetics. In addition, the data gathered will be used to assess how cardiopulmonary bypass (CPB), deep hypothermic cardiac arrest (DHCA), and modified ultrafiltration (MUF) affect tissue penetration of the prophylactically administered cefazolin. The study involves the use of microdialysis (MD) and plasma sampling methods to determine the pharmacokinetic properties of cefazolin when used as a prophylactic antibiotic during the second palliation procedure (superior vena cava-pulmonary anastomosis) for infants with single ventricle physiology. This requires the use of microdialysis (MD) catheters inserted into the left deltoid muscle in eligible subjects after the induction of general anesthesia as well as collection of microdialysate and blood samples throughout the duration of the procedure. Cefazolin will be administered as standard of care. Cefazolin concentrations in the collected samples will be measured via a validated high-performance liquid chromatography (HPLC) and mass spectrometry assay. Pharmacokinetic analyses will be performed.

Official Title
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Skeletal Muscle and Plasma Concentrations of Cefazolin During Pediatric Cardiac Surgery Utilizing Cardiopulmonary Bypass, Deep Hypothermic Cardiac Arrest, and Modified Ultrafiltration

Conditions
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Cava-pulmonary Anastomosis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females with single ventricle physiology undergoing their second palliation procedure (typically performed between 3-6 months of age) Use of cefazolin as the prophylactic antibiotic during the operation Written informed consent provided by the parent or legal guardian Exclusion Criteria: Use of prophylactic antibiotic other than cefazolin during the operation Anatomic or other abnormalities of the upper arm that would preclude insertion of a microdialysis catheter Known renal or hepatic function

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 6 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of Cefazolin | Composite (or Profile) of Pharmacokinetics | predose, .08,.25, .5, 1, 1.5, 2, 3, 4 hours and post dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigate the relationship between cefazolin concentrations in the plasma and those at the level of IF of skeletal muscle | Investigate the effects of CPB, DHCA, and MUF on tissue distribution of cefazolin Determine the concentration of cefazolin in IF of skeletal muscle at different stages of cardiac surgery and compare these values to concentrations of cefazolin needed to be effective against common bacterial organisms causing SSIs Investigate the relationship between cefazolin concentrations in the plasma and those at the level of IF of skeletal muscle. Assess the safety of the use of microdialysis method during pediatric cardiac surgery | One Year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacokinetics, cefazolin, microdialysis sampling, interstitial fluid, skeletal muscle, plasma, children