[A study of second-line antituberculosis drug concentrations and their association with treatment outcomes in patients with multidrug-resistant or rifampicin-resistant tuberculosis].

Authors

M J Liu, Q Qiu, C J Zhao, X B Zheng, D N Li, Y T Han, B B Che, B Xu

Published in

Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi. Volume 47. Issue 6. Pages 1135-1143. Jun 10, 2026.

Abstract

Objective: To understand the distribution and associated factors of second-line antituberculosis drug concentrations in patients with multidrug-resistant or rifampicin-resistant tuberculosis (MDR/RR-TB), and to explore their association with treatment outcomes. Methods: A multi-center prospective cohort study was conducted at three designated tuberculosis hospitals in Nantong and Zhenjiang City, Jiangsu Province, and Jinhua City, Zhejiang Province. Patients with newly diagnosed MDR/RR-TB who received standard treatment between January 2022 and December 2024 were included. After 14 days of treatment, venous blood samples were collected at 2 and 6 hours post-dose to measure the plasma concentrations of linezolid, bedaquiline, clofazimine, levofloxacin, moxifloxacin, cycloserine, and pyrazinamide using a validated liquid chromatography-tandem mass spectrometry method. Demographic, clinical, and laboratory data were collected to investigate the factors associated with plasma drug concentrations, and the relationship between drug concentrations and treatment outcomes was further evaluated. Results: A total of 99 MDR/RR-TB patients were included in this study, with 73.7% being male and a median (Q₁, Q₃) age of 53.6 (37.2, 67.5) years. Pulmonary cavities were observed in 39.4% of patients at baseline. The regimen consisting of bedaquiline, linezolid, fluoroquinolones, cycloserine, and clofazimine was the most frequently prescribed one (44.4%, 44/99). Regarding the drugs, cycloserine (91.9%), linezolid (87.9%), and clofazimine (84.8%) were the most commonly prescribed agents. The median (Q₁, Q₃) values for peak drug concentration (C_max) of linezolid, pyrazinamide, cycloserine, clofazimine, bedaquiline, moxifloxacin, and levofloxacin were 15.000 (11.801, 18.048), 25.988 (22.997, 31.000), 10.604 (7.480, 17.251), 0.662 (0.513, 0.844), 2.290 (1.445, 3.353), 2.591 (2.162, 3.371), 8.550 (6.844, 11.352) mg/L, respectively. Interindividual variability in Cmax was observed across all drugs, with cycloserine, bedaquiline, and moxifloxacin demonstrating particularly high coefficients of variation (all CV >70.0%). Correlation analysis revealed positive relationships between clofazimine and bedaquiline (ρ=0.487, P=0.006) and between levofloxacin and linezolid (ρ=0.571, P=0.004). The dose-to-weight ratio was found to be significantly associated with the concentrations of pyrazinamide (β=0.530, 95%CI: 0.120-0.940, P=0.010), linezolid (β=0.900, 95%CI: 0.250-1.550, P=0.007), cycloserine (β=1.080, 95%CI: 0.350-1.760, P=0.004), and fluoroquinolones (β=0.680, 95%CI: 0.200-1.160, P=0.005), while age was associated with the concentrations of cycloserine (β=0.190, 95%CI: 0.060-0.310, P=0.010), and fluoroquinolones (β=0.060, 95%CI: 0.015-0.105, P=0.009). In addition, hemoglobin levels were associated with the concentrations of cycloserine (β=0.110, 95%CI: 0.015-0.199, P=0.010) and fluoroquinolones (β=-0.050, 95%CI: -0.090--0.020, P=0.002). Although patients who responded to treatment had relatively higher concentrations of pyrazinamide and levofloxacin, these differences were not statistically significant. Conclusions: Plasma concentrations of second-line antituberculosis drugs showed inter-individual variability among patients with MDR/RR-TB. The dose-to-weight ratio was the major factor associated with the drug concentrations, supporting the rationale of weight-based dosing. When deciding the treatment regimen and drug doses, it is important to take into account the potential drug-drug interactions. Therapeutic drug monitoring may contribute to improved MDR/RR-TB treatment outcomes by precise adjustment of drug doses.

PMID:
42373493
Bibliographic data and abstract were imported from PubMed on 30 Jun 2026.

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