title: Cefazolin and linezolid penetration into sternal cancellous bone during coronary artery bypass grafting.
abstract: OBJECTIVE
  Deep sternal wound infection is a severe complication after cardiac surgery. Insufficient antibiotic target site concentrations may account for variable success of perioperative prophylaxis. Therefore, we measured perioperative penetration of cefazolin and of linezolid into sternal cancellous bone after sternotomy in coronary artery bypass grafting (CABG) patients by in vivo microdialysis.
  
  
  METHODS
  Nine patients underwent CABG using a skeletonized left internal mammary artery. Standard antibiotic prophylaxis consisted of 4 g cefazolin prior to skin incision and additional 2 g during skin closure. In addition, 600 mg of linezolid were administered prior to skin incision and after 12 h for study purposes. Two microdialysis probes were inserted into the sternal cancellous bone (left and right side) after sternotomy.
  
  
  RESULTS
  First mean peak cefazolin and linezolid plasma concentrations were 273 ± 92 µg/ml and 22.1 ± 8.9 µg/ml, respectively. Mean peak concentrations of antibiotics in sternal cancellous bone on the left and right sternal side were 112 ± 59 µg/ml and 159 ± 118 µg/ml for cefazolin and 10.9 ± 4.0 µg/ml and 12.6 ± 6.1 µg/ml for linezolid, respectively. Cefazolin exceeded the required tissue concentrations for relevant pathogens by far, but linezolid did not gain effective tissue concentrations in all patients for some relevant pathogens. Mammary artery harvesting had no significant effect on antibiotic tissue penetration.
  
  
  CONCLUSIONS
  Direct measurement of antibiotic concentration in sternal cancellous bone with in vivo microdialysis is technically demanding but safe and feasible. We could demonstrate sufficient antibiotic coverage with our standard cefazolin-dosing regimen in the sternal cancellous bone during cardiac surgery. Mammary artery harvesting had no clinically relevant effect on tissue penetration. Linezolid concentrations were not sufficient for some relevant pathogens.
authors.affiliation: Division of Cardiac Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria martin.andreas@meduniwien.ac.at.
authors.forename: Martin
authors.initials: M
authors.lastname: Andreas
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Zeitlinger
authors.affiliation: Division of Cardiac Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Wisser
authors.affiliation: Department of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Jaeger
authors.affiliation: Department of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Maier-Salamon
authors.affiliation: Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Thalhammer
authors.affiliation: Division of Cardiac Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Alfred
authors.initials: A
authors.lastname: Kocher
authors.affiliation: Division of Cardiothoracic and Vascular Anesthesia & Critical Care Medicine, Department of Anaesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, Austria.
authors.forename: Joerg-Michael
authors.initials: JM
authors.lastname: Hiesmayr
authors.affiliation: Division of Cardiac Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Guenther
authors.initials: G
authors.lastname: Laufer
authors.affiliation: Division of Cardiothoracic and Vascular Anesthesia & Critical Care Medicine, Department of Anaesthesia, General Intensive Care and Pain Management, Medical University of Vienna, Vienna, Austria.
authors.forename: Doris
authors.initials: D
authors.lastname: Hutschala
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019072:Antibiotic Prophylaxis; D002437:Cefazolin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D005260:Female; D006801:Humans; D000069349:Linezolid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008477:Mediastinal Diseases / Q000188:drug therapy*; D008875:Middle Aged; D013249:Sternum / Q000601:surgery*; D013530:Surgical Wound Infection / Q000188:drug therapy*
chemical_list: D000900:Anti-Bacterial Agents; D002437:Cefazolin; D000069349:Linezolid
keywords: Coronary artery bypass grafting; Deep sternal wound infection; Mediastinal infection; Perioperative antibiotics; Wound infection