title: Cefazolin bolus and continuous administration for elective cardiac surgery: improved pharmacokinetic and pharmacodynamic parameters.
abstract: OBJECTIVE
  Cefazolin (1-2 g bolus at induction possibly repeated after cardiopulmonary bypass) remains the standard for antibiotic prophylaxis in cardiac surgery. Data indicate, however, that it is underdosed with this dosing schedule. A prospective, randomized study comparing intermittent versus loading dose plus continuous infusion for the same total dose of cefazolin was performed to assess which modality is pharmacokinetically and pharmacodynamically advantageous.
  
  
  METHODS
  Patients received 2 g cefazolin as a starting dose and then were divided into an intermittent group (receiving another 1 g at 3, 9, and 15 hours after the first dose) and a continuous group (continuous infusion started after the first dose, providing 1 g every 6 hours for 18 hours). Cefazolin levels were measured in blood and atria.
  
  
  RESULTS
  Mean total and calculated free trough concentrations in blood varied greatly among patients in the intermittent group and were lower than those in the continuous group (P < .05 at 15, 18 and 24 hours). For 9 of 10 (90%) patients in the continuous infusion group, the targeted pharmacokinetic and pharmacodynamic goal (time above minimal inhibitory concentration >90%) was achieved, whereas the goal was met for only 3 of 10 (30%) in the intermittent group (P < .05). The mean atrial tissue concentration was also higher with continuous infusion (P < .05).
  
  
  CONCLUSIONS
  Administration of cefazolin as bolus plus continuous infusion has pharmacokinetic and pharmacodynamic advantages relative to intermittent administration. It provides more stable serum levels, lower interpatient variability, and higher myocardial tissue penetration.
authors.affiliation: Section of Anesthesiology and Intensive Care, Department of Critical Care, University of Florence, Firenze, Italy. chiara.adembri@unifi.it
authors.forename: C
authors.initials: C
authors.lastname: Adembri
authors.forename: R
authors.initials: R
authors.lastname: Ristori
authors.forename: C
authors.initials: C
authors.lastname: Chelazzi
authors.forename: S
authors.initials: S
authors.lastname: Arrigucci
authors.forename: M I
authors.initials: MI
authors.lastname: Cassetta
authors.forename: A R
authors.initials: AR
authors.lastname: De Gaudio
authors.forename: A
authors.initials: A
authors.lastname: Novelli
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D019072:Antibiotic Prophylaxis; D006348:Cardiac Surgical Procedures; D002437:Cefazolin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D017558:Elective Surgical Procedures; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D011446:Prospective Studies; D013530:Surgical Wound Infection / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D002437:Cefazolin