Vancomycin and Cefoxitin During Pediatric Cardiopulmonary Bypass

Study Overview
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Brief Summary
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The aim of this study will be to evaluate vancomycin and cefoxitin blood levels during elective cardiopulmonary bypass (CPB) surgery in four pre-determined pediatric strata: neonates, infants, children weighting less than 40 kg and children weighting more than 40 kg.

Detailed Description
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Few data are available in current literature about pharmacokinetics (PK) of antibiotics administered as surgical prophylaxis to children scheduled for cardiac surgery with CPB. In particular, vancomycin PK during CPB has been studied only in small case series, whereas no specific study has been conducted, so far, in the specific setting of children receiving cefoxitin during CPB. CPB affects patients' volemia and drugs PK is eventually altered. On the other side during and after surgery for heart defects, many risk factors may decrease renal and hepatic clearance, including altered renal perfusion, use of vasoactive agents, and use of concomitant nephrotoxic medications. Primary Objective of the study will be: • To study the pharmacokinetic profile of vancomycin and cefoxitin administered, as antibiotic prophylaxis to children undergoing elective CPB. Secondary Objectives will be: To evaluate if a significant difference in blood levels will occur in the four predetermined patients' categories. To evaluate the role of hemodilution during CPB on studied antibiotics' serum concentration To verify the incidence of post-operative infections in the studied population with particular attention to sensitive bacteria To evaluate the impact of ultrafiltration in studied antibiotics' clearance To evaluate safety of the administered antibiotics This is a prospective monocentric, open label, not controlled clinical trial.

Official Title
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Vancomycin and Cefoxitin Levels During Pediatric Cardiac Surgery With Cardiopulmonary Bypass

Conditions
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Congenital Heart Disease

Intervention / Treatment
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* Other: vancomycin pharmacokinetics
* Other: cefoxitin pharmacokinetics


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Elective cardiac surgery schedule with the planned application of CPB Parents of neonates, or their legal representative, able to consent and comply with protocol requirements. Exclusion Criteria: Urgent or emergent surgery Antibiotic therapy (any) administered before surgery Patients receiving, before surgery, any other ofr of extracorporeal treatment (i.e extracorporeal membrane oxygenation, continuous renal replacement therapy) Previous renal or hepatic dysfunction requiring need for antibiotic posology modification. Surgery requiring antibiotic prophylaxis with different drug combinations (i.e vancomycin and gentamycin) extremely low birth weight neonates.

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 18 Years

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| vancomycin and cefoxitin pharmacokinetics<br>This is surgical prophylaxis and cefoxitin/vancomycin have to be administered to each patient of the study, before surgery | Other: vancomycin pharmacokinetics<br>* vancomycin serial plasmatic and ultrafiltrate samples in order to assess plasmatic and ultrafiltrate drug concentrations<br>Other: cefoxitin pharmacokinetics<br>* cefoxitin serial plasmatic and ultrafiltrate samples in order to assess plasmatic and ultrafiltrate drug concentrations<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| vancomycin and cefoxitin concentration change in serial plasmatic samples | a 4-points pharmacokinetic curve per each antibiotic will be generated by serial average plasmatic vancomycin and cefoxitin concentration assessments. | samples will be withdrawn: at skin incision, 15 minutes after CPB start (CPB1), at the end of CPB (CPB2), at end of surgery. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| differences between pre-determined subgroups (neonates, infants, children weighting less than 40 kg and children weighting more than 40 kg) in plasmatic vancomycin and cefoxitin levels change at each time point |  | samples will be withdrawn: at skin incision, 15 minutes after CPB start (CPB1), at the end of CPB (CPB2). | 
| vancomycin and cefoxitin clearance by ultrafiltration | The clearance of vancomycin and cefoxitin in the ultrafiltrate (UF) will be evaluated. Antibiotics' sieving coefficient (SC) will be calculated from antibiotics concentrations at the following time points: UF1/[(CPB1+CPB2)/2]. Antibiotics clearance will be calculated as SC*UF rate (ml/min) | Ultrafiltrate sample will be withdrawn at the end of CPB (UF1) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antibiotic prophylaxis, pharmacokinetics, cardiopulmonary bypass