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Antimicrobial Agents and Chemotherapy, April 2006, p. 1372-1375, Vol. 50, No. 4
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.4.1372-1375.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Impaired Target Site Penetration of Vancomycin in Diabetic Patients following Cardiac Surgery

Keso Skhirtladze,1 Doris Hutschala,1 Tatjana Fleck,2 Florian Thalhammer,3 Marek Ehrlich,2 Thomas Vukovich,4 Markus Müller,5 and Edda M. Tschernko1,5*

Department of Cardiothoracic and Vascular Anesthesia & CCM,1 Department of Cardiothoracic Surgery,2 Department of Infectious Diseases,3 Department of Laboratory Medicine,4 Department of Clinical Pharmacology, University of Vienna, General Hospital, Vienna, Austria5

Received 28 June 2005/ Returned for modification 30 September 2005/ Accepted 13 January 2006

Soft tissue infections constitute a serious complication following surgery in diabetic patients and frequently require the administration of vancomycin. However, despite antibiotic treatment, mortality of patients with postoperative infections remains high and might be related to an impaired penetration of anti-infective agents to target tissues. Therefore, the present study was designed to measure vancomycin tissue concentrations in six diabetic and six nondiabetic patients after cardiac surgery. Vancomycin was administered as a continuous intravenous infusion at an infusion rate of 80 to 120 mg/h. Vancomycin concentrations in soft tissues and plasma were measured in all patients during steady state as "therapeutic window" concentrations in plasma by microdialysis on day 8 ± 4 after initiation of vancomycin treatment. Vancomycin tissue concentrations in diabetic patients were significantly lower than in nondiabetics (3.7 mg/liter versus 11.9 mg/liter; P = 0.002). The median vancomycintissue/vancomycinplasma concentration ratio was 0.1 in diabetic patients and 0.3 in nondiabetics (P = 0.002). Our study demonstrated that vancomycin penetration into target tissues is substantially impaired in diabetic patients versus nondiabetics. Insufficient tissue concentrations could therefore possibly contribute to failure of antibiotic treatment and the development of antimicrobial resistance in diabetic patients.

* Corresponding author. Mailing address: Department of Cardiothoracic and Vascular Anesthesia & CCM, University of Vienna, General Hospital, Waeringer Guertel 18-20, A-1090 Vienna, Austria. Phone: 43-1-40400-4109. Fax: 43-1-40400-4110. E-mail: edda.tschernko{at}meduniwien.ac.at.

Antimicrobial Agents and Chemotherapy, April 2006, p. 1372-1375, Vol. 50, No. 4
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.4.1372-1375.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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