吡嗪酰胺
氯法齐明
利福平
治疗药物监测
基岩
莫西沙星
利福平
抗生素
乙胺丁醇
结核分枝杆菌
药理学
肺结核
医学
抗药性
药品
利奈唑啉
色谱法
化学
微生物学
万古霉素
细菌
生物
免疫学
麻风病
遗传学
克拉霉素
病理
金黄色葡萄球菌
作者
Niklas Köhler,Hande Karaköse,Hans-Peter Grobbel,Doris Hillemann,Sönke Andres,Christina König,Barbara Kalsdorf,Thomas Theo Brehm,Lucas Böttcher,Inna Friesen,Harald Hoffmann,Dražen Strelec,Dagmar Schaub,Charles A. Peloquin,Stefan Schmiedel,Laurent A. Décosterd,Eva Choong,Sebastian G. Wicha,Rob E. Aarnoutse,Christoph Lange,Patricia M. Sánchez Carballo
出处
期刊:Pharmaceutics
[MDPI AG]
日期:2023-10-27
卷期号:15 (11): 2543-2543
被引量:1
标识
DOI:10.3390/pharmaceutics15112543
摘要
The treatment of drug-resistant Mycobacterium tuberculosis relies on complex antibiotic therapy. Inadequate antibiotic exposure can lead to treatment failure, acquired drug resistance, and an increased risk of adverse events. Therapeutic drug monitoring (TDM) can be used to optimize the antibiotic exposure. Therefore, we aimed to develop a single-run multiplex assay using high-performance liquid chromatography-mass spectrometry (HPLC-MS) for TDM of patients with multidrug-resistant, pre-extensively drug-resistant and extensively drug-resistant tuberculosis. A target profile for sufficient performance, based on the intended clinical application, was established and the assay was developed accordingly. Antibiotics were analyzed on a zwitterionic hydrophilic interaction liquid chromatography column and a triple quadrupole mass spectrometer using stable isotope-labeled internal standards. The assay was sufficiently sensitive to monitor drug concentrations over five half-lives for rifampicin, rifabutin, levofloxacin, moxifloxacin, bedaquiline, linezolid, clofazimine, terizidone/cycloserine, ethambutol, delamanid, pyrazinamide, meropenem, prothionamide, and para-amino salicylic acid (PAS). Accuracy and precision were sufficient to support clinical decision making (≤±15% in clinical samples and ±20-25% in spiked samples, with 80% of future measured concentrations predicted to fall within ±40% of nominal concentrations). The method was applied in the TDM of two patients with complex drug-resistant tuberculosis. All relevant antibiotics from their regimens could be quantified and high-dose therapy was initiated, followed by microbiological conversion. In conclusion, we developed a multiplex assay that enables TDM of the relevant first- and second-line anti-tuberculosis medicines in a single run and was able to show its applicability in TDM of two drug-resistant tuberculosis patients.