title: Pharmacokinetic characteristics and microbiologic appropriateness of cefazolin for perioperative antibiotic prophylaxis in elective cardiac surgery.
abstract: Adequate levels of perioperative antibiotic prophylaxis are essential for prevention of surgical site infections. We examined pharmacokinetic details of 2 g cefazolin administered during induction of anesthesia with repeat dosing shortly after initiation of cardiopulmonary bypass (CPB) in cardiac surgery.
  
  
  
  To identify the microbiologic flora targeted with prophylaxis, pre-, and postoperative swabs were taken from sternal skin. Blood samples for measurement of cefazolin were obtained in 24 patients. Drug levels were used for population pharmacokinetic modeling using Nonmem software (Icon Development Solutions, San Antonio, Tex).
  
  
  
  More than 90% of bacteria on sternal skin were sensitive to cefazolin, indicating minimal inhibitory concentrations <8 mg/L. All serum levels of cefazolin were above 8 mg/L and might thus effectively prevent infection. Pharmacokinetic modeling in a 1-compartment model predicted a population mean clearance (CL) of 5.23 L/h and a volume of distribution (Vd) of 15.8 L. CPB increased Vd from 14.4 L to 22.1 L with a consecutive reduction to 18 L after the end of extracorporeal circulation. The final model implemented interindividual variability on CL and Vd, incorporating the covariates CPB and albumin on Vd and creatinine clearance on CL. Goodness-of-fit calculations showed that this model adequately describes the data derived from our clinical cohort.
  
  
  
  Two grams of cefazolin at induction of anesthesia with a repeat dose after initiation of CPB ensures adequate drug levels to target a majority of pathogens of surgical site infections. Pharmacokinetic modeling demonstrated a significant influence of CPB on the volume of distribution and elimination of cefazolin. Other influences on pharmacokinetic parameters were albumin, protein, and creatinine clearance.
authors.affiliation: Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University of Muenster, Muenster, Germany. Electronic address: lanckohr@anit.uni-muenster.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Lanckohr
authors.affiliation: Department of Pharmacy, University of Muenster, Muenster, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Horn
authors.affiliation: Department of Pharmaceutical and Medical Chemistry - Clinical Pharmacy, Westfaelische Wilhelm-University Muenster, Muenster, Germany.
authors.forename: Swantje
authors.initials: S
authors.lastname: Voeller
authors.affiliation: Department of Pharmaceutical and Medical Chemistry - Clinical Pharmacy, Westfaelische Wilhelm-University Muenster, Muenster, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Hempel
authors.affiliation: Department of Laboratory Medicine, University of Muenster, Muenster, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Fobker
authors.affiliation: Department of Cardiac Surgery, University of Muenster, Muenster, Germany.
authors.forename: Henryk
authors.initials: H
authors.lastname: Welp
authors.affiliation: Institute of Medical Microbiology, University of Muenster, Muenster, Germany.
authors.forename: Robin
authors.initials: R
authors.lastname: Koeck
authors.affiliation: Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University of Muenster, Muenster, Germany.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Ellger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019072:Antibiotic Prophylaxis / Q000009:adverse effects / Q000379:methods*; D001419:Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D002437:Cefazolin / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D017558:Elective Surgical Procedures; D005260:Female; D005858:Germany; D006785:Hospitals, University; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008954:Models, Biological; D011446:Prospective Studies; D012867:Skin / Q000382:microbiology*; D013530:Surgical Wound Infection / Q000175:diagnosis / Q000382:microbiology / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D002437:Cefazolin
keywords: NONMEN; cefazolin; perioperative; perioperative prophylaxis; pharmacokinetics