title: In vivo interactions of continuous flucloxacillin infusion and high-dose oral rifampicin in the serum of 15 patients with bone and soft tissue infections due to Staphylococcus aureus - a methodological and pilot study.
abstract: BACKGROUND
  Increased antibiotic resistance against Staphylococcus aureus and low penetration into bone requires regimen optimization of available drugs.
  
  
  METHODS
  We evaluate pharmoacokinetic and pharmacodynamic parameters (PK/PD) as well as in vivo interactions of continuous flucloxacillin 12 g/d administration combined with high dose oral rifampicin 600 mg bid in the serum of 15 adult patients with bone and soft tissue infections. We use the patient's own serum directed against his own isolated S. aureus strain to reproduce in vivo conditions as closely as possible.
  
  
  RESULTS
  The continuous flucloxacillin infusion constantly generated plasma free drug levels largely exceeding the serum minimal inhibitory concentrations (mean 74-fold). Combination with rifampicin significantly increased flucloxacillin levels by 44.5%. Such an increase following rifampicin introduction was documented in 10/15 patients, whereas a decrease was observed in 1/15 patients. Finally, all infections were cured and the combination was well tolerated.
  
  
  CONCLUSIONS
  In this in vivo methodological pilot study among adult patients with orthopaedic infections due to S. aureus, we describe a new method and reveal substantial but inconsistent interactions between flucloxacillin and rifampicin, of which the clinical significance remains unclear.
authors.affiliation: Department of Infectious Diseases, Geneva University Hospitals and Medical School, 4 Rue Gabrielle Perret-Gentil, 1211 Geneva, Switzerland ; Clinic for Infectious Diseases, University of Berne, Inselspital, Bern Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Garzoni
authors.affiliation: Department of Infectious Diseases, Geneva University Hospitals and Medical School, 4 Rue Gabrielle Perret-Gentil, 1211 Geneva, Switzerland ; Orthopaedic Surgery Department, Geneva University Hospitals and Medical School, 4 Rue Gabrielle Perret-Gentil, 1211 Geneva, Switzerland.
authors.forename: Ilker
authors.initials: I
authors.lastname: Uçkay
authors.affiliation: Orthopaedic Surgery Department, Geneva University Hospitals and Medical School, 4 Rue Gabrielle Perret-Gentil, 1211 Geneva, Switzerland.
authors.forename: Wilson
authors.initials: W
authors.lastname: Belaieff
authors.affiliation: Departments of Pharmacokinetics and Clinical Pharmacy, Victor-Segalen University, Bordeaux, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Breilh
authors.affiliation: Orthopaedic Surgery Department, Geneva University Hospitals and Medical School, 4 Rue Gabrielle Perret-Gentil, 1211 Geneva, Switzerland.
authors.forename: Domizio
authors.initials: D
authors.lastname: Suvà
authors.affiliation: Department of Infectious Diseases, Geneva University Hospitals and Medical School, 4 Rue Gabrielle Perret-Gentil, 1211 Geneva, Switzerland.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Huggler
authors.affiliation: Department of Infectious Diseases, Geneva University Hospitals and Medical School, 4 Rue Gabrielle Perret-Gentil, 1211 Geneva, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lew
authors.affiliation: Orthopaedic Surgery Department, Geneva University Hospitals and Medical School, 4 Rue Gabrielle Perret-Gentil, 1211 Geneva, Switzerland.
authors.forename: Pierre
authors.initials: P
authors.lastname: Hoffmeyer
authors.affiliation: Orthopaedic Surgery Department, Geneva University Hospitals and Medical School, 4 Rue Gabrielle Perret-Gentil, 1211 Geneva, Switzerland ; Department of Infectious Diseases, Tours University Hospital, Tours, France.
authors.forename: Louis
authors.initials: L
authors.lastname: Bernard
keywords: Flucloxacillin; Pharmacodynamics; Rifampicin; Staphylococcus aureus; Synergism