Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients

Phase 4

Completed

• Conditions: Congenital Heart Diseases; Aortic Valve Disorder
• Interventions: Drug: Cefazolin 25 mg/kg body weight and Vancomycin hydrochloride; Drug: Cefazolin 30 mg/kg body weight

• Registration Number: NCT01619982
• Lead Sponsor: Stanford University

Brief Summary

The investigators hope to learn 1) if the addition of prophylaxis with vancomycin will decrease the rate of cefazolin non-susceptible surgical site infections (SSI), in high risk population 2) to develop better understanding of vancomycin and cefazolin pharmacokinetics in children undergoing cardiopulmonary bypass (CPB) 3) to assess the barriers to vancomycin dosing peri-operatively 4) to assess side effects and risks associated with peri-operative vancomycin administration. This will allow us to improve patient care by better understanding the benefits or the risks of peri-operative vancomycin administration and potentially decrease cefazolin-resistant surgical site infections.

In addition, this study gives us the opportunity to evaluate cefazolin and vancomycin pharmacokinetics (pK) on children on CPB.

The investigators will take blood samples from 20 patients. In 10 patients the investigators will do Cefazolin pK analysis and in the other 10 the investigators will do pK Vancomycin analysis. For the remainder of 292 patients, only prospective chart review will be done to determine the incidence of SSIs.

This data will be compared with 936 controls who received only Cefazolin pre-operatively as prophylaxis for SSI's.

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Detailed Description

With 100% compliance with the surgical infection prevention (SIP) bundle, the risk of surgical site infections (SSIs) has decreased considerably, but is still greater than the baseline rate at the best comparison hospital (2.5%). Recent analysis of SSI's in cardiovascular surgery patients identified more than half being caused by cefazolin resistant gram positive bacteria (methicillin resistant coagulase negative staphylococci- MRSE (methicillin resistant Staphylococcus epidermidis, or methicillin resistant Staphylococcus aureus- MRSA). Cefazolin is routinely given pre-operatively as surgical prophylaxis in patients undergoing cardiovascular surgery. Vancomycin is not routinely recommended for prophylaxis due to concerns of developing vancomycin resistance, however patients with MRSE and MRSA SSIs end up needing additional surgery to remove or replace infected hardware or grafts and/or additional weeks to months of intravenous vancomycin therapy. This results in significant morbidity to the children and cost to the institution. Several published guidelines suggest the use of pre-operative prophylaxis with vancomycin (alone or in conjunction with cefazolin) in instances where patients may be at higher risk for infection with MRSE or MRSA. The purpose of this study is to determine whether the addition of vancomycin to standard pre-operative prophylaxis with cefazolin in selected high risk subjects along with the full SIP bundle will decrease the incidence of cefazolin-resistant SSI's.

Study Timeline

• Study Start: 2012-02
• Study First Submitted: 2012-03-02
• Study First Submitted QC: 2012-06-14
• Study First Posted: 2012-06-15
• Primary Completion: 2014-12
• Study Completion: 2014-12
• Results First Submitted: 2017-06-21
• Results First Submitted QC: 2017-12-14
• Results First Posted: 2018-01-12
• Status Verified: 2018-04
• Last Update Submitted: 2018-04-16
• Last Update Posted: 2018-05-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

1. Patient less than or equal to 1 year of age who is undergoing cardiovascular surgery requiring CPB or patient under 18 years of age undergoing procedures involving aortic valve or aorta
2. Patients with a positive MRSA screen or a history of MRSA infections who are undergoing any cardiac surgery

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Exclusion Criteria

1. Patients who have known hypersensitivity to vancomycin or cephalosporins
2. Patients with renal insufficiency
3. Patients who have received vancomycin or cephalosporins 48 hours prior to the day of surgery
4. Patients whose surgery is due to an infection-related diagnosis such as endocarditis
5. Patients whose parents do not wish to have them receive vancomycin prophylaxis
6. Neonates born at less than 38 weeks gestational age

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cefazolin 25 mg/kg body weight and vancomycin	Cefazolin 25 mg/kg body weight and Vancomycin hydrochloride	All infants \< 1 year of age with congenital heart diseases requiring cardiac surgery with cardiopulmonary bypass or any patient who requires surgery involving the aorta or the aortic valve will receive both Cefazolin and Vancomycin as preoperative prophylaxis against Surgical Site Infections. This has been recommended in recently published guidelines but not evaluated in children. Intervention: Cefazolin 25 mg/kg body weight and Vancomycin hydrochloride 15 mg/kg body weight
Cefazolin only 30mg/kg body weight	Cefazolin 30 mg/kg body weight	All infants less than one year of age with congenital heart diseases requiring cardiac surgery with cardiopulmonary bypass or all patients who required surgery involving the aorta or the aortic valve received cefazolin 30 mg/kg body weight as preoperative prophylaxis against surgical site infections

Primary Outcome Measures

Name	Time	Method
Number of Patients Who Receive Preoperative Vancomycin and Cefazolin Who Develop a Surgical Site Infection Compared to Those Whose Received Only Cefazolin.	Patients will be monitored for superficial SSIs for 30 days from the date of surgery. Patients will be monitored for 30 days for deep SSIs if no foreign material was implanted and for 1 year if foreign material is present.	Number of patients who receive preoperative vancomycin and cefazolin who develop a surgical site infection (SSI) compared to those whose received only cefazolin. Surveillance was done with standard procedures and definitions.

Secondary Outcome Measures

Name	Time	Method
Cefazolin Pharmacokinetics	Drug levels will be sampled only during the peri-operative time period (0 to 12 hours)	Measured as Elimination Clearance Inter-tissue Clearance (Fast) Inter-tissue Clearance(Slow)
Vancomycin Pharmacokinetics (Plasma Concentration vs Time Curve) in Children During the Peri-operative Period in Infants Undergoing Cardiac Surgery With Cardiopulmonary Bypass (CPB)	Drug levels will be sampled only during the peri-operative time period (0 to 12 hours)	Vancomycin pharmacokinetics measured as Central Volume, Peripheral Volume (Fast), Peripheral Volume (Slow)
Count of Participants Experiencing Adverse Events Commonly Associated With Peri-operative Vancomycin Prophylaxis	Adverse events to vancomycin will be assessed on each patient in the study during the time the patient is in the operating room (0-<24 hours)	Will evaluate for vancomycin associated pre or intraoperative adverse events: 1. Hypotension requiring treatment; 2. Rash, flushing or Red Man's syndrome; 3. Other changes in vital signs (decrease in baseline 02 sat, increased heart or respiratory rate, elevated body temperature) felt to be associated with vancomycin administration; 4. An event associated with vancomycin administration which results in delay in surgery
Vancomycin Pharmacokinetics (Plasma Concentration vs Time Curve) in Children on Cardiopulmonary Bypass (CPB)	Drug levels will be sampled only during the peri-operative time period (0 to 12 hours)	Vancomycin pharmacokinetics measured as Elimination Clearance, Inter-tissue Clearance (Fast), Inter-tissue Clearance (Slow).

Trial Locations

Locations (1)

Lucile Packard Children's Hospital at Stanford; 🇺🇸 Palo Alto, California, United States