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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

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 a...

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Autores principales: Garzoni, Christian, Uçkay, Ilker, Belaieff, Wilson, Breilh, Dominique, Suvà, Domizio, Huggler, Elzbieta, Lew, Daniel, Hoffmeyer, Pierre, Bernard, Louis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072877/
https://www.ncbi.nlm.nih.gov/pubmed/25019039
http://dx.doi.org/10.1186/2193-1801-3-287
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author Garzoni, Christian
Uçkay, Ilker
Belaieff, Wilson
Breilh, Dominique
Suvà, Domizio
Huggler, Elzbieta
Lew, Daniel
Hoffmeyer, Pierre
Bernard, Louis
author_facet Garzoni, Christian
Uçkay, Ilker
Belaieff, Wilson
Breilh, Dominique
Suvà, Domizio
Huggler, Elzbieta
Lew, Daniel
Hoffmeyer, Pierre
Bernard, Louis
author_sort Garzoni, Christian
collection PubMed
description 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.
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spelling pubmed-40728772014-07-11 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 Garzoni, Christian Uçkay, Ilker Belaieff, Wilson Breilh, Dominique Suvà, Domizio Huggler, Elzbieta Lew, Daniel Hoffmeyer, Pierre Bernard, Louis Springerplus Research 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. Springer International Publishing 2014-06-07 /pmc/articles/PMC4072877/ /pubmed/25019039 http://dx.doi.org/10.1186/2193-1801-3-287 Text en © Garzoni et al.; licensee Springer. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.
spellingShingle Research
Garzoni, Christian
Uçkay, Ilker
Belaieff, Wilson
Breilh, Dominique
Suvà, Domizio
Huggler, Elzbieta
Lew, Daniel
Hoffmeyer, Pierre
Bernard, Louis
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
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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072877/
https://www.ncbi.nlm.nih.gov/pubmed/25019039
http://dx.doi.org/10.1186/2193-1801-3-287
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