Pharmacokinetics of Daptomycin During Cardiopulmonary Bypass Surgery
Condition: Late Effects of Surgery; Staphylococcus Aureus; Surgical Site Infection
MeSH terms: Surgical Wound Infection
Study type: Interventional
Phase: Phase 3

Summary: 
      This investigation is a prospective, open-label pharmacokinetic study of daptomycin
      prophylaxis in patients undergoing coronary artery bypass graft surgery without valvular
      replacement.
    

Detailed description: 
      Cardiothoracic surgery is a commonly performed procedure in the United States. Many sites
      previously used cefazolin, an antibiotic, as standard prophylaxis to prevent surgical site
      infections. However, given most bacteria causing surgical site infections are now resistant
      to cefazolin, most center are using vancomycin, an alternative antibiotic, as surgical
      antibiotic prophylaxis. However, some patients cannot take vancomycin, and there are no well
      studied alternatives to vancomycin for surgical prophylaxis. Therefore, we are studying
      daptomycin, a newer United States Food and Drug Administration (FDA)-approved antibiotic, as
      prophylaxis against surgical site infections among patients undergoing cardiothoracic bypass
      (CPB) with coronary artery bypass graft surgery (CABG). Our study will not be powered to see
      if daptomycin is as effective as vancomycin at preventing surgical site infections. Instead,
      the purpose of this study is to validate that adequate levels of antibiotics are present in
      patients' blood during cardiothoracic bypass surgery.

      Study subjects in the intervention group will be followed from the time of enrollment in the
      study until their discharge from the hospital, or up to 7 days following administration of
      daptomycin, whichever comes first.

      The first 15 subjects enrolled will receive the intervention drug daptomycin as surgical
      antibiotic prophylaxis and the following 15 subjects will be enrolled as matched controls and
      will receive the standard of care surgical prophylaxis per the patient's treating physicians.
      The controls will undergo monitoring for the same safety outcomes that the patients who
      received daptomycin will undergo.

      Subjects enrolled in the intervention group will receive a single intravenous administration
      of daptomycin 8 milligram (mg)/kilogram (kg) 30-60 minutes prior to surgery (incision). Blood
      samples will be drawn by the Research Coordinator. A total of 85 (milliliters) mL of blood
      will be collected during the study. A total of 14 blood samples will be collected: 4 samples
      at the Pre-CPB phase, 4 samples during the CPB procedure, and 6 samples Post-CPB. Total
      plasma daptomycin concentrations will be determined utilizing standard high-performance
      liquid chromatography techniques. Plasma concentrations will be compared to the minimum
      inhibitory concentrations (MIC90) of the common pathogens involved in surgical site
      infections, specifically Staphylococcus aureus and coagulase negative Staphylococcus.
    

Intervention name(s): daptomycin
Intervention type(s): Drug
Intervention description(s): Subjects enrolled in the intervention group will receive a single intravenous administration of daptomycin 8 mg/kg 30-60 minutes prior to surgery (incision). The 500 mg vial will be reconstituted with 10 mL of 0.9% normal saline (NS) and further diluted in 50 mL of 0.9% NS to be given over a 30 minute infusion.
Other intervention name(s): Cubicin
Intervention MeSH terms: Daptomycin
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Daptomycin; Antibiotic Prophylaxis; Pharmacokinetics; Surgical Wound Infection; Staphylococcus aureus; Cardiopulmonary Bypass Surgery