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Evaluation of current dosing guidance for oral rifampicin treatment in adult patients with osteoarticular infections
Author(s) -
Marsot Amélie,
Ménard Amélie,
Dupouey Julien,
Allanioux Laurent,
Blin Olivier,
Guilhaumou Romain
Publication year - 2020
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.14319
Subject(s) - dosing , rifampicin , medicine , pharmacokinetics , fusidic acid , pharmacodynamics , pharmacology , antibiotics , minimum inhibitory concentration , population , antibacterial agent , regimen , area under the curve , staphylococcus aureus , microbiology and biotechnology , biology , tuberculosis , pathology , environmental health , bacteria , genetics
For management of osteoarticular infections, rifampicin appears to be the key antibiotic. We aimed to evaluate the actual rifampicin dosing regimens using a population pharmacokinetic model of rifampicin in patients with osteoarticular infections. A Monte Carlo simulation study was performed to simulate steady‐state plasma concentrations for 1000 randomly sampled subjects using a total daily dose between 600 and 1200 mg (600 and 900 mg once daily, 450 and 600 mg twice daily, or 300 mg 3 times daily). When rifampicin was administered with fusidic acid, the pharmacokinetic/pharmacodynamic (PK/PD) target (area under the curve/minimum inhibitory concentration ≥952) was achieved with all tested dosing regimen, except 600 mg once daily for Staphylococcus epidermidis infections. Without coadministration of fusidic acid, none of tested dosing regimens achieved this PK/PD target. Most recommended drug‐dosing regimens allow attaining the fixed area under the curve/minimum inhibitory concentration target for Staphylococcus aureus and coagulase‐negative staphylococcal osteoarticular infections. In future studies, PK/PD target for osteoarticular infections in human should also be confirmed.