Linezolid presents strong antimicrobial activity against multidrug-resistant (MDR) pulmonary tuberculosis (TB), whereas its application in osteoarticular tuberculosis treatment remains understudied. Our objective was to analyze the bone penetration efficiency of linezolid in osteoarticular TB patients.
Osteoarticular TB patients, treated with 600mg q24h linezolid-containing regimens and undergoing surgery, were prospectively and consecutively enrolled. One dose linezolid was administered before surgery. Blood and bone samples were collected simultaneously during operation, and then their linezolid concentrations were detected by performing high-performance liquid chromatography-tandem mass spectrometry. Pus samples were subjected to mycobacterial culture and GeneXpert MTB/RIF assay. The minimum inhibition concentrations (MICs) and drug susceptibility testing were performed with the recovered isolates.
36 eligible osteoarticular TB patients were enrolled, including five MDR/rifampicin-resistant cases. All of the 12 recovered isolates had MICs ≤0.5 μg/mL for linezolid. Mean concentrations in plasma, collected 100-510 min post the preoperative dosing, were 10.43 ± 4.83 μg/mL (range 3.29-22.26 μg/mL) and median concentrations in bone were 3.93 μg/mL (range 0.61-16.34 μg/mL). The median bone/plasma penetration ratio was 0.42 (range 0.14-0.95 μg/mL). Linezolid concentration in bone had linear correlation with the drug concentration in plasma (r = 0.7873, p < 0.0001), while plasma concentration could explain 61.98% of the variation of concentration in bone (R = 0.6198). Notably, stratification analysis by sampling time demonstrated that samples collected 200-510 mins after dosing had very good linear relationship between bone and plasma concentrations (r = 0.9323).
Linezolid penetrates from blood to bone efficiently, and the penetration further stabilizes ∼3 h after dosing.

Copyright © 2020. Published by Elsevier Ltd.