Abstract：
The burden of Mycobacterium avium complex (MAC) lung disease is increasing globally and treatment outcome is in general poor. Therapeutic drug monitoring has the potential to improve treatment outcome by ensuring adequate drug exposure. However, very limited population-based studies exist for MAC lung disease. This study aims to describe the distribution of drug exposure for key antimycobacterial drugs at population level, and to analyse them in relationship to treatment outcome in patients with MAC lung disease.
A prospective cohort aiming to include 100 adult patients diagnosed with and treated for MAC lung disease will be conducted in Shanghai Pulmonary Hospital, China. Blood samples will be collected after 1 month MAC treatment for measurement of macrolides, rifamycin, ethambutol, amikacin and/or fluoroquinolones, using a validated liquid-chromatography tandem mass spectrometry method. Respiratory samples will be collected at inclusion and once every 3 months for mycobacterial culture until treatment completion. Minimum inhibitory concentration (MIC) determination will be performed using a commercial broth microdilution plate. In addition to mycobacterial culture, disease severity and clinical improvement will be assessed from the perspective of lung function, radiological presentation and self-reported quality of life. Whole genome sequencing will be performed for any longitudinal isolates with significant change of MIC to explore the emergence of drug resistance-conferring mutations. The relationship between drug exposure and treatment outcome will be analysed and potential confounders will be considered for adjustment in multivariable models. Meanwhile, the associations between drug exposure in relation to MIC and markers of treatment response will be explored using Cox proportional hazards or binary logistic regression models, as appropriate.
This study has been approved by the ethics committee of Shanghai Pulmonary Hospital (No. K22-149Z). Written and oral informed consent will be obtained from all participants. The study results will be submitted to a peer-reviewed journal.
NCT05824988.
A prospective cohort aiming to include 100 adult patients diagnosed with and treated for MAC lung disease will be conducted in Shanghai Pulmonary Hospital, China. Blood samples will be collected after 1 month MAC treatment for measurement of macrolides, rifamycin, ethambutol, amikacin and/or fluoroquinolones, using a validated liquid-chromatography tandem mass spectrometry method. Respiratory samples will be collected at inclusion and once every 3 months for mycobacterial culture until treatment completion. Minimum inhibitory concentration (MIC) determination will be performed using a commercial broth microdilution plate. In addition to mycobacterial culture, disease severity and clinical improvement will be assessed from the perspective of lung function, radiological presentation and self-reported quality of life. Whole genome sequencing will be performed for any longitudinal isolates with significant change of MIC to explore the emergence of drug resistance-conferring mutations. The relationship between drug exposure and treatment outcome will be analysed and potential confounders will be considered for adjustment in multivariable models. Meanwhile, the associations between drug exposure in relation to MIC and markers of treatment response will be explored using Cox proportional hazards or binary logistic regression models, as appropriate.
This study has been approved by the ethics committee of Shanghai Pulmonary Hospital (No. K22-149Z). Written and oral informed consent will be obtained from all participants. The study results will be submitted to a peer-reviewed journal.
NCT05824988.
摘要：
背景：在全球范围内，鸟分枝杆菌复杂（MAC）肺病的负担正在增加，治疗结果普遍较差。治疗药物监测有可能通过确保适当的药物暴露来改善治疗结果。然而,关于MAC肺病的基于人群的研究非常有限。本研究旨在描述人群水平的关键抗分枝杆菌药物暴露的分布。并分析它们与MAC肺病患者治疗结果的关系。
方法：将在上海肺科医院进行前瞻性队列研究，旨在纳入100名诊断为MAC肺病并接受治疗的成年患者。中国。将在1个月MAC治疗后收集血样用于测量大环内酯类，利福霉素,乙胺丁醇,阿米卡星和/或氟喹诺酮类药物，使用经过验证的液相色谱串联质谱法。将在包含时收集呼吸道样品，每3个月一次用于分枝杆菌培养，直到治疗完成。将使用商业肉汤微量稀释板进行最小抑制浓度(MIC)测定。除了分枝杆菌培养，将从肺功能的角度评估疾病的严重程度和临床改善，放射学表现和自我报告的生活质量。将对具有显著变化的MIC的任何纵向分离株进行全基因组测序,以探索赋予耐药性的突变的出现。将分析药物暴露与治疗结果之间的关系，并考虑潜在的混杂因素，以调整多变量模型。同时,将使用Cox比例风险或二元逻辑回归模型探索药物暴露与MIC和治疗反应标志物之间的关联，视情况而定。
背景：本研究已获得上海市肺科医院伦理委员会的批准（编号：K22-149Z)。将获得所有参与者的书面和口头知情同意书。研究结果将提交给同行评审的期刊。
背景：NCT05824988。
方法：将在上海肺科医院进行前瞻性队列研究，旨在纳入100名诊断为MAC肺病并接受治疗的成年患者。中国。将在1个月MAC治疗后收集血样用于测量大环内酯类，利福霉素,乙胺丁醇,阿米卡星和/或氟喹诺酮类药物，使用经过验证的液相色谱串联质谱法。将在包含时收集呼吸道样品，每3个月一次用于分枝杆菌培养，直到治疗完成。将使用商业肉汤微量稀释板进行最小抑制浓度(MIC)测定。除了分枝杆菌培养，将从肺功能的角度评估疾病的严重程度和临床改善，放射学表现和自我报告的生活质量。将对具有显著变化的MIC的任何纵向分离株进行全基因组测序,以探索赋予耐药性的突变的出现。将分析药物暴露与治疗结果之间的关系，并考虑潜在的混杂因素，以调整多变量模型。同时,将使用Cox比例风险或二元逻辑回归模型探索药物暴露与MIC和治疗反应标志物之间的关联，视情况而定。
背景：本研究已获得上海市肺科医院伦理委员会的批准（编号：K22-149Z)。将获得所有参与者的书面和口头知情同意书。研究结果将提交给同行评审的期刊。
背景：NCT05824988。
