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Antimicrobial Agents and Chemotherapy, February 2005, p. 650-655, Vol. 49, No. 2
0066-4804/05/$08.00+0 doi:10.1128/AAC.49.2.650-655.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Pharmacokinetics and Pharmacodynamics of Cefpirome in Subcutaneous Adipose Tissue of Septic Patients
Robert Sauermann,1 Georg Delle-Karth,2 Claudia Marsik,1 Ilka Steiner,1 Markus Zeitlinger,1 Bernhard X. Mayer-Helm,1 Apostolos Georgopoulos,3 Markus Müller,1 and Christian Joukhadar1,3,4*Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics,1 Department of Internal Medicine II, Intensive Care Unit,2 Department of Internal Medicine I, Division of Infectious Diseases and Chemotherapy,3 Institute of Pharmacology, Medical University of Vienna, Vienna, Austria4
Received 4 May 2004/ Returned for modification 1 August 2004/ Accepted 11 October 2004
The objective of the present study was to evaluate whether cefpirome, a member of the latest class of broad-spectrum cephalosporins, sufficiently penetrates subcutaneous adipose tissue in septic patients. After the administration of the drug at 2 g, tissue cefpirome concentrations in septic patients (n = 11) and healthy controls (n = 7) were determined over a period of 4 h by means of microdialysis. To assess the antibacterial effect of cefpirome at the target site, the measured pharmacokinetic profiles were simulated in vitro with select strains of Staphylococcus aureus and Pseudomonas aeruginosa. The tissue penetration of cefpirome was significantly impaired in septic patients compared with that in healthy subjects. For subcutaneous adipose tissue, the area under the concentration-versus-time curve values from 0 to 240 min were 13.11 ± 5.20 g · min/liter in healthy subjects and 6.90 ± 2.56 g · min/liter in septic patients (P < 0.05). Effective bacterial growth inhibition was observed in all in vitro simulations. This was attributed to the significantly prolonged half-life in tissue (P < 0.05), which kept the tissue cefpirome levels above the MICs for relevant pathogens for extended periods in the septic group. By consideration of a dosing interval of 8 h, the values for the time above MIC (T > MIC) in tissue were greater than 60% for pathogens for which the MIC was 
4 mg/liter in all septic patients. The present data indicate that cefpirome is an appropriate agent for the treatment of soft tissue infections in septic patients. However, due to the high interindividual variability of the pharmacokinetics of cefpirome in tissue, dosing intervals of not more than 8 h should be preferred to ensure that susceptible bacterial strains are killed in each patient.
* Corresponding author. Mailing address: Department of Clinical Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. Phone: 43-1-40400-2981. Fax: 43-1-40400-2998. E-mail: christian.joukhadar{at}meduniwien.ac.at.
Antimicrobial Agents and Chemotherapy, February 2005, p. 650-655, Vol. 49, No. 2
0066-4804/05/$08.00+0 doi:10.1128/AAC.49.2.650-655.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
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