title: Linezolid concentrations in infected soft tissue and bone following repetitive doses in diabetic patients with bacterial foot infections.
abstract: The present study aimed at assessing unbound extracellular concentrations of linezolid in inflamed soft tissue and bone of diabetic patients suffering from severe bacterial foot infections. Linezolid was administered intravenously twice daily at a dosage of 600 mg. At steady-state conditions, the microdialysis technique was utilised to sample serially interstitial space fluid from inflamed subcutaneous adipose tissue and metatarsal bone from 0-8h post dose in three representative patients. Mean peak concentrations of free linezolid in plasma, healthy subcutis, inflamed subcutis and cancellous bone were 16.6+/-3.0, 15.5+/-2.5, 15.8+/-2.8 and 15.1+/-4.1mg/L, respectively. The degree of tissue penetration as expressed by the ratio of the area under the concentration-time curve of free linezolid from 0-12h (fAUC(0-12)) in tissue to the fAUC(0-12) in plasma was 1.32+/-0.09, 1.12+/-0.22 and 1.09+/-0.11 for healthy subcutis, inflamed subcutis and bone, respectively. Based on currently available pharmacokinetic/pharmacodynamic targets, we conclude that linezolid administered at 600 mg twice daily may be considered an effective treatment in diabetic patients suffering from bacterial foot infection complicated by osteomyelitis.
authors.affiliation: J&P Medical Research Ltd., Vienna, Austria.
authors.forename: Friederike
authors.initials: F
authors.lastname: Traunmüller
authors.forename: Michael V
authors.initials: MV
authors.lastname: Schintler
authors.forename: Stephan
authors.initials: S
authors.lastname: Spendel
authors.forename: Martin
authors.initials: M
authors.lastname: Popovic
authors.forename: Oliver
authors.initials: O
authors.lastname: Mauric
authors.forename: Erwin
authors.initials: E
authors.lastname: Scharnagl
authors.forename: Christian
authors.initials: C
authors.lastname: Joukhadar
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001424:Bacterial Infections / Q000188:drug therapy*; D001842:Bone and Bones / Q000737:chemistry*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D017719:Diabetic Foot / Q000150:complications*; D006801:Humans; D000069349:Linezolid; D008297:Male; D008875:Middle Aged; D010019:Osteomyelitis / Q000188:drug therapy; D023303:Oxazolidinones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010949:Plasma / Q000737:chemistry; D012867:Skin / Q000737:chemistry*; D018461:Soft Tissue Infections / Q000188:drug therapy
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid