JAC Advance Access originally published online on July 3, 2009
Journal of Antimicrobial Chemotherapy 2009 64(3):574-578; doi:10.1093/jac/dkp230
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Original research |
High fosfomycin concentrations in bone and peripheral soft tissue in diabetic patients presenting with bacterial foot infection
1 Department of Surgery, Division of Plastic Surgery, Medical University of Graz, Auenbruggerplatz 29, A-8036 Graz, Austria 2 J&P MEDICAL RESEARCH LTD, Auhofstrasse 15/8-9, A-1130 Vienna, Austria 3 Department of Radiology, Division of Cardiovascular and Interventional Radiology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria 4 Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA 5 Harvard Medical School, Boston, MA 02115, USA
Received 6 May 2009; returned 14 May 2009; revised 8 June 2009; accepted 9 June 2009
* Corresponding author. J&P MEDICAL RESEARCH LTD, Auhofstrasse 15/8-9, A-1130 Vienna, Austria. Tel: +43-1-8760432-10; Fax: +43-1-8760432-33; E-mail: christian.joukhadar{at}jp-medical-research.com
Objectives: Appropriate antimicrobial therapy and surgical intervention may be required in diabetic patients presenting with severe bacterial foot infection. Methicillin-resistant Staphylococcus aureus (MRSA) agents such as fosfomycin are increasingly in demand because of recent concern regarding vancomycin and daptomycin efficacy and constant use. Intravenous fosfomycin is approved for the therapy of severe soft tissue infections and is highly active against methicillin-susceptible S. aureus and MRSA. In the present study we investigated fosfomycin's ability to penetrate bone tissue in diabetic patients suffering from severe bacterial foot infection.
Patients and methods: The well established microdialysis technique was utilized to determine fosfomycin concentrations in metatarsal bone in nine patients scheduled for partial bone resection due to bacterial foot infection and osteomyelitis. Plasma and unaffected subcutaneous adipose tissue served as reference compartments.
Results: After a single intravenous dose of approximately 100 mg of fosfomycin per kg of body weight, the mean Cmax, Tmax and AUC0–6 for bone were 96.4 mg/L, 3.9 h and 330.0 mg · h/L, respectively. The degree of tissue penetration as determined by the ratios of the AUC0–6 for bone to plasma and for subcutaneous adipose tissue to plasma were 0.43 ± 0.04 and 0.76 ± 0.05, respectively.
Conclusions: On the basis of relevant pharmacokinetic–pharmacodynamic indices, it seems that fosfomycin is an effective antibiotic for the treatment of deep-seated diabetic foot infections with osseous matrix involvement.
Keywords: single-dose pharmacokinetics , diabetic foot infection , MRSA , osteomyelitis
Michael V. Schintler and Friederike Traunmüller contributed equally to this article.