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Garzoni C, Uçkay I, Belaieff W, et al. 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. Springerplus. 2014;3:287doi: 10.1186/2193-1801-3-287.
Garzoni, C., Uçkay, I., Belaieff, W., Breilh, D., Suvà, D., Huggler, E., Lew, D., Hoffmeyer, P., & Bernard, L. (2014). 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. SpringerPlus, 3287. https://doi.org/10.1186/2193-1801-3-287
Garzoni, Christian, et al. "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." SpringerPlus vol. 3 (2014): 287. doi: https://doi.org/10.1186/2193-1801-3-287
Garzoni C, Uçkay I, Belaieff W, Breilh D, Suvà D, Huggler E, Lew D, Hoffmeyer P, Bernard L. 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. Springerplus. 2014 Jun 07;3:287. doi: 10.1186/2193-1801-3-287. eCollection 2014. PMID: 25019039; PMCID: PMC4072877.
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Springerplus. 2014 Jun 07;3:287. doi: 10.1186/2193-1801-3-287. eCollection 2014.

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.

SpringerPlus

Christian Garzoni, Ilker Uçkay, Wilson Belaieff, Dominique Breilh, Domizio Suvà, Elzbieta Huggler, Daniel Lew, Pierre Hoffmeyer, Louis Bernard

Affiliations

  1. 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.
  2. 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.
  3. Orthopaedic Surgery Department, Geneva University Hospitals and Medical School, 4 Rue Gabrielle Perret-Gentil, 1211 Geneva, Switzerland.
  4. Departments of Pharmacokinetics and Clinical Pharmacy, Victor-Segalen University, Bordeaux, France.
  5. Department of Infectious Diseases, Geneva University Hospitals and Medical School, 4 Rue Gabrielle Perret-Gentil, 1211 Geneva, Switzerland.
  6. 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.

PMID: 25019039 PMCID: PMC4072877 DOI: 10.1186/2193-1801-3-287

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.

Keywords: Flucloxacillin; Pharmacodynamics; Rifampicin; Staphylococcus aureus; Synergism

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