Bone penetration of linezolid in osteoarticular tuberculosis patients of China

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 T...

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Main Authors: Shu’an Wen, Tingting Zhang, Xia Yu, Weijie Dong, Tinglong Lan, Jun Fan, Yi Xue, Fen Wang, Lingling Dong, Shibing Qin, Hairong Huang
Format: Article
Language:English
Published: Elsevier 2021-02-01
Series:International Journal of Infectious Diseases
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1201971220325194
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author Shu’an Wen
Tingting Zhang
Xia Yu
Weijie Dong
Tinglong Lan
Jun Fan
Yi Xue
Fen Wang
Lingling Dong
Shibing Qin
Hairong Huang
author_facet Shu’an Wen
Tingting Zhang
Xia Yu
Weijie Dong
Tinglong Lan
Jun Fan
Yi Xue
Fen Wang
Lingling Dong
Shibing Qin
Hairong Huang
author_sort Shu’an Wen
collection DOAJ
description 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 (R2 = 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.
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spelling doaj.art-0ff73e289da142e396a4e40682fa1ea02022-12-21T19:38:55ZengElsevierInternational Journal of Infectious Diseases1201-97122021-02-01103364369Bone penetration of linezolid in osteoarticular tuberculosis patients of ChinaShu’an Wen0Tingting Zhang1Xia Yu2Weijie Dong3Tinglong Lan4Jun Fan5Yi Xue6Fen Wang7Lingling Dong8Shibing Qin9Hairong Huang10National 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, ChinaNational 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, ChinaNational 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, ChinaDepartment of Orthopedics, Beijing Chest Hospital, Capital Medical University, Beijing, ChinaDepartment of Orthopedics, Beijing Chest Hospital, Capital Medical University, Beijing, ChinaDepartment of Orthopedics, Beijing Chest Hospital, Capital Medical University, Beijing, ChinaNational 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, ChinaNational 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, ChinaNational 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, ChinaDepartment of Orthopedics, Beijing Chest Hospital, Capital Medical University, Beijing, China; Corresponding authors.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; Corresponding authors.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 (R2 = 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.http://www.sciencedirect.com/science/article/pii/S1201971220325194Osteoarticular tuberculosisLinezolidPlasmaBoneDrug penetration
spellingShingle Shu’an Wen
Tingting Zhang
Xia Yu
Weijie Dong
Tinglong Lan
Jun Fan
Yi Xue
Fen Wang
Lingling Dong
Shibing Qin
Hairong Huang
Bone penetration of linezolid in osteoarticular tuberculosis patients of China
International Journal of Infectious Diseases
Osteoarticular tuberculosis
Linezolid
Plasma
Bone
Drug penetration
title Bone penetration of linezolid in osteoarticular tuberculosis patients of China
title_full Bone penetration of linezolid in osteoarticular tuberculosis patients of China
title_fullStr Bone penetration of linezolid in osteoarticular tuberculosis patients of China
title_full_unstemmed Bone penetration of linezolid in osteoarticular tuberculosis patients of China
title_short Bone penetration of linezolid in osteoarticular tuberculosis patients of China
title_sort bone penetration of linezolid in osteoarticular tuberculosis patients of china
topic Osteoarticular tuberculosis
Linezolid
Plasma
Bone
Drug penetration
url http://www.sciencedirect.com/science/article/pii/S1201971220325194
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