Expert consensus on therapy and drug monitoring clinical application of anti-tuberculosis drug (updated in 2025)

doi:10.19982/j.issn.1000-6621.20250435

Abstract

Abstract:

Therapeutic drug monitoring (TDM) is a method to develop individualized dosing regimens for patients based on the measurement of drug exposure pharmacological biomarkers, or efficacy indicators in the body, using quantitative pharmacological models and taking the drug treatment window as the benchmark. Its core is individualized drug therapy. In order to further guide and standardize the TDM work of anti-tuberculosis drugs in Chinese medical institutions, ensuring scientific rigor, ethical practice, and standardized procedures for maximal patient benefit, Pharmaceutical Professional Branch of Chinese Antituberculosis Association, in conjunction with Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute systematically updated the indications, monitoring methods, dose adjustment, and application in special populations of TDM on the basis of the 2021 Expert consensus on clinical application of therapeutic drug monitoring for anti-tuberculosis drugs. This consensus is registered on the international practice guidelines platform, and the formulation process follows the principles of methodology. Drawing on the collaborative expertise of tuberculosis pharmaceutical and clinical experts, along with the latest evidence-based research and practical experience, this consensus will provide scientific and feasible guidance for the clinical implementation of TDM.

Key words: Tuberculosis, Drug monitoring, Therapeutic uses, Guidebooks

CLC Number:

R978.3

Pharmaceutical Professional Branch of Chinese Antituberculosis Association. Expert consensus on therapy and drug monitoring clinical application of anti-tuberculosis drug (updated in 2025)[J]. Chinese Journal of Antituberculosis, 2026, 48(2): 167-187. doi: 10.19982/j.issn.1000-6621.20250435

Figures/Tables 3

特殊人群分类	TDM核心目标	重点监测药物与关键策略	TDM关键阈值与剂量调整	临床管理要点
糖尿病与结核病共病	确保有效暴露,预防因低暴露导致的获得性耐药。以RFP达标为首要目标	药物:RFP、INH、PZA、Mfx 策略:治疗早期(稳态第3~5天)常规进行。采用服药后2h、6h两点采样估算AUC	若RFP C_max<8mg/L或AUC/MIC<435,可将剂量上调至15~20mg/kg,并于1 周后复查TDM	?对高BMI、胃肠功能障碍者,应增加TDM频次 ?口服降糖药(如磺脲类、DPP-4抑制剂)与RFP存在显著相互作用,会导致降糖疗效减弱或失效
并发HIV 感染	管理复杂DDIs,确保抗结核与抗病毒治疗双重有效	药物:RFP、INH、Lzd及抗逆转录病毒药物,如DTG、EFV、RAL 策略:在强化期同步监测。强烈建议优先对CD4<200个/μl、低体质量指数(<18.5kg/m²)、肝功能异常或并发机会性感染者开展TDM监测	利福霉素类药物: 联用DTG:DTG 50mg,1次/d,调整为2次/d;停用RFP后维持用药约2 周。DTG与RFB合用无需调整DTG剂量;联用RAL:800mg,2次/d;联用EFV:EFV无须加量,Rfb调整为600mg,1次/d;蛋白酶抑制剂(PI/r):避免联用RFP,改用Rfb Lzd:与齐多夫定均存在骨髓毒性,避免联用 INH:在CYP2B6慢/中等代谢表型人群中,INH可抑制EFV清除	?临床判读:需综合CYP2B6等代谢表型、肝功能指标进行动态优化
肝功能异常	平衡肝毒性风险与治疗疗效,防止肝损伤恶化并保证治疗强度	药物:PZA、RFP、INH 策略:以AUC为核心,从治疗早期即开始监测,并每周复查肝酶直至稳定。合并HCV治疗者需并行TDM	警戒阈值: PZA:AUC_0~24h>363mg·h^-1·L^-1 RFP:AUC_0~24h>271mg·h^-1·L^-1 INH:C_2h>6mg/L,慢乙酰化(NAT2)与INH肝损伤风险显著相关	?出现肝功能异常时,依据TDM结果优先采取减量或延长给药间隔,而非盲目停药 ?存在肝损伤(ALT>3 ULN)时尽量避免使用PZA
肾功能异常	避免经肾排泄药物蓄积中毒,依据肾功能精准调整	药物:EMB、PZA、氨基糖苷类、CS 策略:以C_min和AUC为核心。依据GFR及RRT方式/频率制定给药方案	警戒阈值: EMB:C_max>6mg/L 氨基糖苷类:C_min<1~2mg/L,疗效保证C_max/MIC>8~10 Cs:C_max 20~35mg/L, C_min 10~20mg/L	?透析后需补充给药,尤其是氨基糖苷类和环丝氨酸。对于氨基糖苷类药物,需实施个体化给药,通过延长给药间隔,以保证疗效
儿童和青少年	克服年龄相关PK差异,确保有效暴露并预防成长发育期毒性	药物:RFP、INH、EMB、PZA及二线药(LZD、Bdq) 策略:常规实施。优先覆盖<5岁低龄儿童或营养不良(BMI<15kg/m²)者。采用C_2h和有限采样法估算AUC	疗效阈值: RFP:C_max>8mg/L;INH:C_2h 3~6mg/L,NAT2快乙酰化型患儿,可依据TDM上调剂量至7~10mg·kg^-1·d^-1);PZA:AUC_0-24h>363mg·h^-1·L^-1 警戒阈值: Lzd: C_min>2mg/L	?儿童不同年龄阶段吸收/分布/代谢/排泄差异显著,暴露变异度大,易出现低暴露或毒性难以早期识别,早期开展TDM可同时评估疗效与潜在毒性
老年患者	应对增龄性生理变化及多重用药带来的复杂PK/PD变异,平衡疗效与安全性,预防药物蓄积中毒	药物:所有抗结核药物,重点监测经肾排泄的EMB、PZA、Lzd以及治疗窗窄的药物策略:治疗初期常规实施。以C_min监测预防蓄积,结合AUC评估总体暴露。需全面评估肝肾功能、合并用药及营养状况	疗效阈值: INH:C_2h 3~6mg/L RFP:C_max≥8mg/L PZA:C_max<35mg/L与失败相关、<58mg/L与痰转阴延迟相关警戒阈值: EMB:C_max>6mg/L LZD:C_min>2mg/L	?安全监测:强化对肝肾功能、血常规、尿酸及视觉症状的监测,注意区别毒性迹象与衰老症状 ?若C_min超过目标范围上限或出现毒性迹象,应优先考虑延长给药间隔而非简单减量,以维持峰值浓度保证疗效
妊娠期女性	应对妊娠期PK变化,保障母婴安全	药物:RFP、INH、Lzd、Lfx、Bdq 策略:治疗初期常规实施,以AUC/MIC达标为核心。动态监测母婴药物水平	疗效阈值: RFP:AUC/MIC≥271 Lfx:AUC/MIC>146 剂量调整:妊娠期RFP、Lfx、Bdq暴露偏低,需依据TDM结果上调剂量,产后及时复查并调整治疗剂量	?应用INH需注意母婴维生素B6与肝功能监测 ?应用Lzd注意观察婴儿胃肠道及念珠菌感染相关表现 ?Bdq在乳汁中显著蓄积,若继续母乳喂养需个体化评估与监测

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