中国骨关节结核患者中利奈唑胺的骨穿透性。

Bone penetration of linezolid in osteoarticular tuberculosis patients of China.

机构信息

National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China.

Department of Orthopedics, Beijing Chest Hospital, Capital Medical University, Beijing, China.

出版信息

Int J Infect Dis. 2021 Feb;103:364-369. doi: 10.1016/j.ijid.2020.11.203. Epub 2020 Dec 2.

DOI:10.1016/j.ijid.2020.11.203

PMID:33278623

Abstract

BACKGROUND

Linezolid presents strong antimicrobial activity against multidrug-resistant (MDR) pulmonary tuberculosis (TB), but its application in osteoarticular tuberculosis treatment remains understudied. Our objective was to analyze the bone penetration efficiency of linezolid in osteoarticular TB patients.

METHODS

Osteoarticular TB patients, treated with 600 mg q 24 h 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 their linezolid concentrations were then detected using 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.

RESULTS

A total of 36 eligible osteoarticular TB patients were enrolled, including five MDR/rifampicin-resistant cases. All the 12 recovered isolates had MICs ≤0.5 μg/mL for linezolid. Mean concentrations in plasma, collected 100-510 min after 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 a 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 min after dosing had very good linear relationships between their bone and plasma concentrations (r = 0.9323).

CONCLUSIONS

Linezolid penetrates from blood to bone efficiently, and the penetration further stabilizes ∼3 h after dosing.

摘要

背景

利奈唑胺对耐多药（MDR）肺结核（TB）具有很强的抗菌活性，但在骨关节结核治疗中的应用仍研究不足。我们的目的是分析利奈唑胺在骨关节结核患者中的骨穿透效率。

方法

前瞻性连续纳入接受 600mg q24h 利奈唑胺方案治疗且接受手术的骨关节结核患者。手术前给予一剂利奈唑胺。在手术过程中同时采集血液和骨样本，并使用高效液相色谱-串联质谱法检测其利奈唑胺浓度。脓液样本进行分枝杆菌培养和 GeneXpert MTB/RIF 检测。对回收的分离物进行最低抑菌浓度（MIC）和药敏试验。

结果

共纳入 36 例符合条件的骨关节结核患者，其中包括 5 例 MDR/利福平耐药病例。所有 12 株回收分离株的利奈唑胺 MIC 值均≤0.5μg/mL。术前给药后 100-510 分钟采集的血浆中平均浓度为 10.43±4.83μg/mL（范围 3.29-22.26μg/mL），骨中中位数浓度为 3.93μg/mL（范围 0.61-16.34μg/mL）。骨/血浆穿透比中位数为 0.42（范围 0.14-0.95μg/mL）。骨中利奈唑胺浓度与血浆中药物浓度呈线性相关（r=0.7873，p<0.0001），而血浆浓度可解释骨中浓度变化的 61.98%（R=0.6198）。值得注意的是，按采样时间分层分析表明，给药后 200-510 分钟采集的样本，其骨和血浆浓度之间具有很好的线性关系（r=0.9323）。