title: Pharmacokinetics and pharmacodynamics of cefpirome in subcutaneous adipose tissue of septic patients.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Sauermann
authors.forename: Georg
authors.initials: G
authors.lastname: Delle-Karth
authors.forename: Claudia
authors.initials: C
authors.lastname: Marsik
authors.forename: Ilka
authors.initials: I
authors.lastname: Steiner
authors.forename: Markus
authors.initials: M
authors.lastname: Zeitlinger
authors.forename: Bernhard X
authors.initials: BX
authors.lastname: Mayer-Helm
authors.forename: Apostolos
authors.initials: A
authors.lastname: Georgopoulos
authors.forename: Markus
authors.initials: M
authors.lastname: Müller
authors.forename: Christian
authors.initials: C
authors.lastname: Joukhadar
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D019540:Area Under Curve; D002511:Cephalosporins / Q000009:adverse effects / Q000493:pharmacokinetics*; D020374:Chromatography, Micellar Electrokinetic Capillary; D015169:Colony Count, Microbial; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D017551:Microdialysis; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D018805:Sepsis / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000187:drug effects; D000097572:Cefpirome
chemical_list: D002511:Cephalosporins; D000097572:Cefpirome