Clinical trial NCT01619982: Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
Official title: Effect of Pre-operative Prophylaxis With Vancomycin on Rate of Cefazolin Non-susceptible Gram Positive Surgical Site Infections in Cardiovascular Surgery Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Congenital Heart Diseases
Aortic Valve Disorder
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2012-06-15
Enrollment: 32
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Patients Who Receive Preoperative Vancomycin and Cefazolin Who Develop a Surgical Site Infection Compared to Those Whose Received Only Cefazolin.
timeFrame: 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.
Secondary outcomes:
measure: Cefazolin Pharmacokinetics
timeFrame: Drug levels will be sampled only during the peri-operative time period (0 to 12 hours)
measure: Cefazolin Pharmacokinetics
timeFrame: Drug levels will be sampled only during the peri-operative time period (0 to 12 hours)
measure: Vancomycin Pharmacokinetics (Plasma Concentration vs Time Curve) in Children During the Peri-operative Period in Infants Undergoing Cardiac Surgery With Cardiopulmonary Bypass (CPB)
timeFrame: Drug levels will be sampled only during the peri-operative time period (0 to 12 hours)
measure: Vancomycin Pharmacokinetics (Plasma Concentration vs Time Curve) in Children on Cardiopulmonary Bypass (CPB)
timeFrame: Drug levels will be sampled only during the peri-operative time period (0 to 12 hours)
measure: Count of Participants Experiencing Adverse Events Commonly Associated With Peri-operative Vancomycin Prophylaxis
timeFrame: 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)
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital at Stanford
state: California
Study officials:
affiliation: Stanford University
name: Kathleen Gutierrez, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for prevention of surgical site infection, 1999. Hospital Infection Control Practices Advisory Committee. Infect Control Hosp Epidemiol. 1999 Apr;20(4):250-78; quiz 279-80. doi: 10.1086/501620. No abstract available.
citation: Ingrande J, Gutierrez K, Lemmens HJ, Verma A, Nicolau DP, Sutherland CA, Ramamoorthy C. Pharmacokinetics of Cefazolin and Vancomycin in Infants Undergoing Open-Heart Surgery With Cardiopulmonary Bypass. Anesth Analg. 2019 May;128(5):935-943. doi: 10.1213/ANE.0000000000003876.