title: Pharmacokinetic and dynamic study of levofloxacin and rifampicin in bone and joint infections.
abstract: OBJECTIVE
  We studied the pharmacokinetic and pharmacodynamic parameters of levofloxacin and rifampicin in bone and joint infections. The optimal dose regimen of these two antibiotics has not been documented yet.
  
  
  METHODS
  We performed plasma dosage for each antibiotic in patients with a bone and joint infection requiring treatment with a levofloxacin and rifampicin combination. We then computed the 6 hours post dose area under the concentration-time curve (AUC(0-6h)), the peak plasma concentration (Cmax), the area under the inhibitory concentration curve (AUIC), and the peak-to-minimum-inhibitory-concentration ratio (Cmax/MIC). The pharmacodynamic results were then compared to the published thresholds of effectiveness. The doses used were levofloxacin 500 mg bid and rifampicin 20mg/kg per day.
  
  
  RESULTS
  The plasma of 17 patients was dosed. The average AUC(0-6h) for levofloxacin was 46.59 mg.h/l, the average Cmax 10.7 mg/l, the average AUIC 932, and the average Cmax/MIC 107.5. The averages for rifampicin were 42.2mg.h/l, 11.8 mg/l, 11,125 and 1514. Given that bone concentration of levofloxacin is 30% that of the plasma concentration, that concentration was divided by three to estimate bone concentration.
  
  
  CONCLUSIONS
  The optimal thresholds of pharmacodynamic effectiveness were obtained for most patients with levofloxacin at 500 mg bid. Additional studies are still required to determine the optimal rifampicin dose.
authors.affiliation: Service de Maladies Infectieuses, Centre Hospitalier de la Région d'Annecy, 1 Avenue de l'Hôpital, Metz Tessy, BP 90074, 74374 Pringy cedex, France. mathildeguillaume@hotmail.com
authors.forename: M
authors.initials: M
authors.lastname: Guillaume
authors.forename: R
authors.initials: R
authors.lastname: Garraffo
authors.forename: M
authors.initials: M
authors.lastname: Bensalem
authors.forename: C
authors.initials: C
authors.lastname: Janssen
authors.forename: S
authors.initials: S
authors.lastname: Bland
authors.forename: J
authors.initials: J
authors.lastname: Gaillat
authors.forename: J-P
authors.initials: JP
authors.lastname: Bru
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D019540:Area Under Curve; D001170:Arthritis, Infectious / Q000188:drug therapy*; D015992:Body Mass Index; D015299:Discitis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005593:Fracture Fixation, Internal; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D064704:Levofloxacin; D008297:Male; D008875:Middle Aged; D009140:Musculoskeletal Diseases / Q000139:chemically induced; D015242:Ofloxacin / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D010000:Osteitis / Q000188:drug therapy*; D011446:Prospective Studies; D016459:Prosthesis-Related Infections / Q000188:drug therapy; D012293:Rifampin / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D058566:Sacroiliitis / Q000188:drug therapy; D013203:Staphylococcal Infections / Q000188:drug therapy; D013530:Surgical Wound Infection / Q000188:drug therapy
chemical_list: D000900:Anti-Bacterial Agents; D064704:Levofloxacin; D015242:Ofloxacin; D012293:Rifampin