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Updated: Jul 10, 2026
A Novel Method to Determine the Longitudinal Antibacterial Activity of Drug-Eluting Materials
Published on: March 3, 2023
In vivo microdialysis to measure antibiotic penetration into soft tissue during cardiac surgery
Doris Hutschala1, Keso Skhirtladze, Christian Kinstner
1Department of Cardiothoracic Anesthesia and Intensive Care Medicine, University of Vienna, General Hospital, Vienna, Austria.
Background:
Wound infections remain an important problem after cardiac surgery despite antimicrobial prophylaxis, causing increased mortality, morbidity, and costs. Penetration properties of antibiotics are altered by extracorporeal circulation, fluid resuscitation, surgery, and postoperative treatment measures. So far, interstitial antibiotic concentration has not been measured continuously during surgery. It remains uncertain whether the concentration of the prophylactic antibiotic is sufficient in interstitial tissue. Therefore, we measured interstitial concentrations of cefazolin in vivo during cardiac surgery.
Methods:
Seven patients undergoing aortic valve replacement were studied in this prospective, observational, pharmacokinetic study. Cefazolin, 4 g, was administered before skin incision and additionally 2 g during skin closure. Microdialysis, an in vivo approach, was used to measure unbound interstitial drug concentrations.
Results:
Cefazolin plasma concentration rose to a peak of 443 microg/mL (range, 169 to 802 microg/mL) within 20 minutes (range, 20 to 40 minutes). The maximum of interstitial concentration of cefazolin was observed within 60 minutes after antibiotic administration. Cefazolin tissue levels exceeded minimum inhibitory concentration values for most potential wound pathogens for more than 600 minutes after infusion. The maximum drug concentration of cefazolin in subcutaneous interstitial fluid was 22.6% of maximum plasma levels, comparable with 19.4% in muscular tissue.
Conclusions:
Cefazolin, administered in the high dose used at our institution, is effective for prevention against infection with the most prevalent pathogens during and immediately after cardiac surgery. Additionally, our data show that it is important to reevaluate clinical dosing schemas by means of direct in vivo measurements.
Insights
High-dose cefazolin effectively prevents wound infections after cardiac surgery. Continuous in vivo measurements confirmed sufficient interstitial antibiotic concentrations, supporting current dosing strategies.
Area of Science:
- Pharmacokinetics and antimicrobial therapy in cardiac surgery.
- In vivo drug concentration monitoring.
- Surgical site infection prevention.
Background:
- Wound infections are a significant complication after cardiac surgery, increasing patient morbidity and healthcare costs.
- Antibiotic efficacy can be compromised by surgical factors affecting drug penetration into tissues.
- Interstitial antibiotic concentrations during surgery are not well understood.
Purpose of the Study:
- To measure interstitial cefazolin concentrations in vivo during cardiac surgery.
- To assess the adequacy of prophylactic antibiotic levels in surgical wound tissues.
- To inform clinical dosing strategies based on direct measurements.
Main Methods:
- Prospective, observational pharmacokinetic study involving seven patients undergoing aortic valve replacement.
- Administration of cefazolin (4g pre-incision, 2g at closure).
- In vivo microdialysis used to quantify unbound interstitial cefazolin concentrations.
Main Results:
- Peak plasma cefazolin concentrations reached 443 microg/mL within 20 minutes.
- Maximum interstitial cefazolin concentrations were observed within 60 minutes post-administration.
- Tissue cefazolin levels exceeded minimum inhibitory concentrations for key pathogens for over 600 minutes.
Conclusions:
- High-dose cefazolin is effective in preventing infections from common pathogens during and after cardiac surgery.
- Direct in vivo measurements highlight the importance of re-evaluating current clinical dosing regimens.
- Sufficient interstitial antibiotic concentrations support the efficacy of the administered cefazolin dose.
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