Aortic Valve Disorder, Congenital Heart Diseases
Conditions
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. \--------------------------------------------------------------------------------
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.
Interventions
DRUGCefazolin 25 mg/kg body weight and Vancomycin hydrochloride
Cefazolin 25 mg/kg/dose administered intravenously over 5 minutes within 60 minutes of surgical incision and then re-dosed (25 mg/kg: maximum 2 grams/dose) every 4 hours intra-operatively depending on the duration of surgery as per standard peri-operative prophylaxis for cardiac surgery and Vancomycin 15 mg/kg (max 1.5 gram/dose) will be administered intravenously over 1-2 hours (after completion of cefazolin infusion) For patients younger than 1 month of age, a one-time repeat dose of 15 mg/kg can be given intraoperatively 12 hours after the beginning of the first vancomycin dose if the procedure is \> 12 hours in duration. For patients equal to or older than 1 month, a one-time repeat dose of 15 mg/kg (max 1.5 grams) will be given intra-operatively 8 hours after the beginning of the first vancomycin dose if the procedure is \> 8 hours in duration.
DRUGCefazolin 30 mg/kg body weight
Intervention: Drug: Cefazolin pre-operative prophylaxis Other Names: Cefazolin: Brand Names Ancef, Kefzol Cefazolin 30 mg/kg/dose administered intravenously over 10 minutes within 60 minutes of surgical incision and then re-dosed (30 mg/kg: maximum 2 grams/dose) every 4 hours intra-operatively depending on the duration of surgery as per standard peri-operative prophylaxis for cardiac surgery.
Sponsors
Stanford University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 18 Years
Healthy volunteers
No
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
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Cefazolin Pharmacokinetics | Drug levels will be sampled only during the peri-operative time period (0 to 12 hours) | Cefazolin Pharmacokinetics was measured as Central Volume, Peripheral Volume (Fast), Peripheral Volume (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) |
| 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). |
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cefazolin 25 mg/kg Body Weight and Vancomycin Cefazolin 25 mg/kg/dose administered intravenously over 10 minutes within 60 minutes of surgical incision and then re-dosed (25 mg/kg: maximum 2 grams/dose) every 4 hours intra-operatively depending on the duration of surgery as per standard peri-operative prophylaxis for cardiac surgery.
Vancomycin hydrochloride: Vancomycin 15 mg/kg (max 1.5 gram/dose) will be administered intravenously over 1-2 hours (after completion of cefazolin infusion). Repeat same dose intraoperatively at 8 hours or at 12 hours if patient younger than 1 month of age. | 20 |
| Cefazolin 30 mg/kg Body Weight Cefazolin 30 mg/kg/dose administered intravenously over 10 minutes within 60 minutes of surgical incision and then re-dosed (30 mg/kg: maximum 2 grams/dose) every 4 hours intra-operatively depending on the duration of surgery as per standard peri-operative prophylaxis for cardiac surgery. | 12 |
| Total | 32 |
Baseline characteristics
| Characteristic | Cefazolin 25 mg/kg Body Weight and Vancomycin | Cefazolin 30 mg/kg Body Weight | Total |
|---|---|---|---|
| Age, Customized 0 day to 12 months | 20 Participants | 12 Participants | 32 Participants |
| Sex: Female, Male Female | 12 Participants | 8 Participants | 20 Participants |
| Sex: Female, Male Male | 8 Participants | 4 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 12 |
| other Total, other adverse events | 0 / 20 | 0 / 12 |
| serious Total, serious adverse events | 0 / 20 | 0 / 12 |
Outcome results
Primary
Number of Patients Who Receive Preoperative Vancomycin and Cefazolin Who Develop a Surgical Site Infection Compared to Those Whose Received Only Cefazolin.
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.
Time frame: 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.
Population: Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients undergoing cardiopulmonary bypass
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cefazolin 25mg/kg Body Weight and Vancomycin | Number of Patients Who Receive Preoperative Vancomycin and Cefazolin Who Develop a Surgical Site Infection Compared to Those Whose Received Only Cefazolin. | 0 participants |
| Cefazolin 30mg/kg Body Weight | Number of Patients Who Receive Preoperative Vancomycin and Cefazolin Who Develop a Surgical Site Infection Compared to Those Whose Received Only Cefazolin. | 0 participants |
Secondary
Cefazolin Pharmacokinetics
Cefazolin Pharmacokinetics was measured as Central Volume, Peripheral Volume (Fast), Peripheral Volume (Slow)
Time frame: Drug levels will be sampled only during the peri-operative time period (0 to 12 hours)
Population: Cefazolin pharmacokinetics were assessed only in the Cefazolin 30 mg/kg Body Weight group
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cefazolin 30mg/kg Body Weight | Cefazolin Pharmacokinetics | Central Volume | 0.547 L |
| Cefazolin 30mg/kg Body Weight | Cefazolin Pharmacokinetics | Peripheral Volume (Fast) | 0.102 L |
| Cefazolin 30mg/kg Body Weight | Cefazolin Pharmacokinetics | Peripheral Volume (slow) | 0.7 L |
Secondary
Cefazolin Pharmacokinetics
Measured as Elimination Clearance Inter-tissue Clearance (Fast) Inter-tissue Clearance(Slow)
Time frame: Drug levels will be sampled only during the peri-operative time period (0 to 12 hours)
Population: Cefazolin pharmacokinetics were assessed only in the Cefazolin 30 mg/kg Body Weight group
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cefazolin 30mg/kg Body Weight | Cefazolin Pharmacokinetics | Elimination clearance | 0.00396 L/min |
| Cefazolin 30mg/kg Body Weight | Cefazolin Pharmacokinetics | Inter-tissue Clearance (Fast) | 0.1 L/min |
| Cefazolin 30mg/kg Body Weight | Cefazolin Pharmacokinetics | Inter-tissue Clearance (slow) | 0.0231 L/min |
Secondary
Count of Participants Experiencing Adverse Events Commonly Associated With Peri-operative Vancomycin Prophylaxis
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
Time frame: 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)
Population: Only the Cefazolin 25 mg/kg Body Weight and Vancomycin groups were assessed, the Cefazolin 30mg/kg body weight did not receive vancomycin
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cefazolin 25mg/kg Body Weight and Vancomycin | Count of Participants Experiencing Adverse Events Commonly Associated With Peri-operative Vancomycin Prophylaxis | 0 Participants |
Secondary
Vancomycin Pharmacokinetics (Plasma Concentration vs Time Curve) in Children During the Peri-operative Period in Infants Undergoing Cardiac Surgery With Cardiopulmonary Bypass (CPB)
Vancomycin pharmacokinetics measured as Central Volume, Peripheral Volume (Fast), Peripheral Volume (Slow)
Time frame: Drug levels will be sampled only during the peri-operative time period (0 to 12 hours)
Population: Vancomycin pharmacokinetics were assessed only in the Cefazolin 25 mg/kg body weight and Vancomycin arm
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cefazolin 25mg/kg Body Weight and Vancomycin | Vancomycin Pharmacokinetics (Plasma Concentration vs Time Curve) in Children During the Peri-operative Period in Infants Undergoing Cardiac Surgery With Cardiopulmonary Bypass (CPB) | Central Volume | 0.901 L |
| Cefazolin 25mg/kg Body Weight and Vancomycin | Vancomycin Pharmacokinetics (Plasma Concentration vs Time Curve) in Children During the Peri-operative Period in Infants Undergoing Cardiac Surgery With Cardiopulmonary Bypass (CPB) | Peripheral Volume (Fast) | 1.02 L |
| Cefazolin 25mg/kg Body Weight and Vancomycin | Vancomycin Pharmacokinetics (Plasma Concentration vs Time Curve) in Children During the Peri-operative Period in Infants Undergoing Cardiac Surgery With Cardiopulmonary Bypass (CPB) | Peripheral Volume (Slow) | 1.81 L |
Secondary
Vancomycin Pharmacokinetics (Plasma Concentration vs Time Curve) in Children on Cardiopulmonary Bypass (CPB)
Vancomycin pharmacokinetics measured as Elimination Clearance, Inter-tissue Clearance (Fast), Inter-tissue Clearance (Slow).
Time frame: Drug levels will be sampled only during the peri-operative time period (0 to 12 hours)
Population: Vancomycin pharmacokinetics were assessed only in the Cefazolin 25 mg/kg body weight and Vancomycin arm
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cefazolin 25mg/kg Body Weight and Vancomycin | Vancomycin Pharmacokinetics (Plasma Concentration vs Time Curve) in Children on Cardiopulmonary Bypass (CPB) | Elimination Clearance | 0.00695 L/min |
| Cefazolin 25mg/kg Body Weight and Vancomycin | Vancomycin Pharmacokinetics (Plasma Concentration vs Time Curve) in Children on Cardiopulmonary Bypass (CPB) | Inter-tissue Clearance (Fast) | 0.0554 L/min |
| Cefazolin 25mg/kg Body Weight and Vancomycin | Vancomycin Pharmacokinetics (Plasma Concentration vs Time Curve) in Children on Cardiopulmonary Bypass (CPB) | Inter-tissue Clearance (Slow) | 0.0202 L/min |