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Abstract：
Patients with Mycobacterium intracellulare pulmonary disease are more likely to experience poor treatment outcomes if they have been observed with microbiological persistence after 6 months of treatment. This study aims to identify the risk factors for microbiological persistence and describe the changes in the minimum inhibitory concentration (MIC) during antimycobacterial treatment. This retrospective case-control study enrolled patients diagnosed with M. intracellulare pulmonary disease between April 2017 and September 2021 at Shanghai Pulmonary Hospital. Patients with positive cultures after 6 months of treatment (positive group) were matched by age and sex in a 1:1 ratio to patients with negative conversion (negative group). Totally, 46 pairs of patients were analyzed. Risk factors for microbiological persistence at month 6 were smoking, previous tuberculosis treatment, chronic lung diseases, a positive baseline acid-fast bacilli smear, and adverse drug reactions; the risk was reduced by a regimen containing ethambutol, ≥3 effective drugs, and a higher pre-treatment absolute lymphocyte count. Regarding the drug-resistance profile, the negative group had a higher proportion of susceptibility to clarithromycin (100.0% vs 84.8%, P = 0.012). Most isolates were susceptible or intermediate to amikacin in both groups (93.5% and 84.8%, respectively). Nine patients (16.4%, 9/55) had a change in the drug-resistance profile, including four who changed from clarithromycin susceptible to clarithromycin resistant, and the other three reversed. Two pairs of isolates had a change in resistance to amikacin. In conclusion, risk factors for microbiological persistence were identified, and the change in MIC values during antimycobacterial treatment indicated the need for monitoring to enable timely adjustment of the regimen.IMPORTANCENontuberculous mycobacteria pulmonary disease (NTM-PD) has been recognized as an important public health issue because of its increasing incidence globally, low cure rate, and high recurrence rate. NTM-PD has innate resistance to many first-line anti-tuberculous drugs, which limits the treatment options. Mycobacterium intracellulare is reportedly the most important pathogenic NTM and accounts for the highest proportion of NTM-PD in China. A previous study suggested that poor microbiological response after 6 months of treatment is predictive of treatment failure. The present study investigated the risk factors associated with persistent positive sputum cultures by treatment month 6 in patients with M. intracellulare pulmonary disease and the variation in minimum inhibitory concentration patterns in clinical settings. This information might help to identify patients at higher risk of treatment failure and enable the timely provision of necessary interventions.
摘要：
如果在6个月的治疗后观察到微生物持久性，患有细胞内分枝杆菌肺病的患者更有可能经历不良的治疗结果。本研究旨在确定微生物持久性的危险因素，并描述抗分枝杆菌治疗期间最小抑制浓度（MIC）的变化。这项回顾性病例对照研究纳入了2017年4月至2021年9月在上海市肺科医院诊断为细胞内分枝杆菌肺病的患者。治疗6个月后培养阳性的患者（阳性组）按年龄和性别以1：1的比例与阴性转换的患者（阴性组）相匹配。完全正确,对46对患者进行分析。第6个月微生物持续的危险因素是吸烟，以前的结核病治疗，慢性肺病,基线抗酸杆菌涂片呈阳性,和药物不良反应；含有乙胺丁醇的方案降低了风险，≥3种有效药物，和较高的治疗前绝对淋巴细胞计数。关于耐药性，阴性组对克拉霉素的敏感性较高（100.0％vs84.8％，P=0.012)。两组中大多数分离株对阿米卡星敏感或处于中间水平(93.5%和84.8%,分别)。9名患者（16.4%，9/55）的耐药性发生了变化，其中4人由克拉霉素易感转为克拉霉素耐药,其他三个颠倒了。两对分离株对阿米卡星的耐药性发生了变化。总之,确定了微生物持久性的危险因素，抗分枝杆菌治疗期间MIC值的变化表明需要进行监测以及时调整治疗方案.重要结核分枝杆菌肺病(NTM-PD)因其在全球范围内的发病率不断增加,已被认为是一个重要的公共卫生问题。治愈率低，和高复发率。NTM-PD对许多一线抗结核药物具有先天抗性，这限制了治疗选择。据报道，胞内分枝杆菌是最重要的致病性NTM，在中国占NTM-PD的比例最高。先前的研究表明，治疗6个月后微生物反应不良是治疗失败的预测因素。本研究调查了在治疗第6个月时与细胞内分枝杆菌肺病患者持续痰培养阳性相关的危险因素，以及临床环境中最低抑制浓度模式的变化。这些信息可能有助于识别治疗失败风险较高的患者，并能够及时提供必要的干预措施。
