Evaluation of current dosing guidance for oral rifampicin treatment in adult patients with osteoarticular infections. Issue 11 (13th May 2020)

• Record Type: Journal Article
• Authors: Marsot, Amélie; Ménard, Amélie; Dupouey, Julien; Allanioux, Laurent; Blin, Olivier; Guilhaumou, Romain
• Is Part Of: British journal of clinical pharmacology. Volume 86:Issue 11(2020)
• Page Start: 2319
• Page End: 2324
• Publication Date: 2020-05-13
• Subjects: fusidic acid -- osteoarticular infections -- pharmacokinetic -- rifampicinc -- simulations; Pharmacology -- Periodicals; Drugs -- Periodicals; 615.1
• DOI: 10.1111/bcp.14319
• Languages: English
• ISSNs: 0306-5251

Abstract

Abstract : 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.