Development of a dosing-adjustment tool for fluoroquinolones in osteoarticular infections: The Fluo-pop study

Biomedicine & Pharmacotherapy

Jean-Baptiste Foulquier¹  Pierre Tattevin²  Fabien Fily²  Vincent Jullien³  Jean-Louis Polard⁴  Bruno Laviolle⁴  Denis Huten⁵  Marie-Clémence Verdier⁶  Matthieu Revest⁷  Cédric Arvieux⁸  Eric Bellissant⁸  Camille Tron⁸  Antoine Petitcollin⁹  Florian Lemaitre⁹  Emmanuelle Comets^1,10 

[1]Correspondence to: Department of Pharmacology, Rennes University Hospital, 2, rue Henri Le Guilloux CEDEX, 35033 Rennes, France.

[2]INSERM, Centre d’Investigation Clinique, CIC 1414, F-35000 Rennes, France

[3]Infectious Diseases Unit, Broussais Hospital, Saint Malo, France

[4]Infectious Diseases and Intensive Care Unit, Pontchaillou University Hospital, Rennes, France

[5]Molecular Mycology Unit-CNRS UMR 2000, Pasteur Institute, 75015 Paris, France

[6]University of Rennes, Inserm, BRM (Bacterial Regulatory RNAs and Medicine), UMR, France

[7]Epicentre, 55 rue Crozatier, 75012, Paris, France

[8]INSERM, Centre d’Investigation Clinique, CIC 1414, F-35000 Rennes, France

[9]Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000 Rennes, France

[10]University Paris 13, groupe hospitalier Paris Seine-Saint-Denis, Assistance publique-Hôpitaux de Paris, 93000 Bobigny, France

关键词: Ofloxacin;    Pharmacokinetics;    Bone infection;    Joint infection;    Modeling;   

DOI  :  

来源: DOAJ

【 摘 要 】

Fluoroquinolones efficacy depend on both the drug exposure and the level of drug resistance of the bacteria responsible for the infection. Specifically for the Staphylococcus species, which is the microorganism mainly involved in osteoarticular infections (OAI), in-vitro data reported that an AUC/MIC ratio above 115 h maximizes drug efficacy. However, data on OAI patients are lacking and a simple approach to access AUCs is still a clinical issue. We conducted a prospective, single-center study in 30 OAI patients hospitalized in the Rennes University Hospital to model ofloxacin pharmacokinetics and to define a limited sampling strategy (LSS) suitable for ofloxacin and levofloxacin treatments. Modeling was conducted with the Monolix software. The final model was externally validated using levofloxacin data. Monte-Carlo simulations were used to evaluate the probability of target attainment (PTA) of different dosing regimens. Two hundred and ninety-seven (297) ofloxacin concentrations were available for the pharmacokinetic modeling. Ofloxacin pharmacokinetics was best described using a bicompartmental model with a first order elimination, and a transit compartment model absorption. CKD-EPI and sex explained half of ofloxacin pharmacokinetic variability. For LSS, the 0, 1 h and 3 h sampling scheme resulted in the best approach both for BID and TID dosages (R2 adjusted = 91.1% and 95.0%, outliers = 4.8% and 5.0%, respectively). PTA allows choosing the best drug and dosage according to various hypotheses. A simple 3-sample protocol (pre-dose, 1 h after intake and 3 h after intake) to estimate ofloxacin and levofloxacin AUC allows optimal drug dosage for the treatment of osteoarticular infections.

【 授权许可】

Unknown