Luo Xuejiao, Zheng Xubin, Fang Yong, Yu Fangyou, Cui Haiyan, Sun Qin, Sha Wei
Department of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Clinical and Research Center for Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
Microbiol Spectr. 2023 Sep 25;11(5):e0080523. doi: 10.1128/spectrum.00805-23.
Patients with 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 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%, = 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. 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 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.
如果患有肺部疾病的患者在治疗6个月后仍存在微生物学持续性感染，那么他们更有可能经历较差的治疗结果。本研究旨在确定微生物学持续性感染的危险因素，并描述抗分枝杆菌治疗期间最低抑菌浓度（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月期间在上海肺科医院被诊断为肺部疾病的患者。治疗6个月后培养结果为阳性的患者（阳性组）按年龄和性别1:1配比与培养结果转阴的患者（阴性组）进行匹配。总共分析了46对患者。治疗6个月时微生物学持续性感染的危险因素包括吸烟、既往结核病治疗史、慢性肺部疾病、基线抗酸杆菌涂片阳性以及药物不良反应；含乙胺丁醇的治疗方案、≥3种有效药物以及较高的治疗前绝对淋巴细胞计数可降低风险。关于耐药谱，阴性组对克拉霉素的敏感比例更高（100.0%对84.8%，P = 0.012）。两组中大多数分离株对阿米卡星敏感或中介（分别为93.5%和84.8%）。9例患者（16.4%，9/55）的耐药谱发生了变化，其中4例从克拉霉素敏感变为克拉霉素耐药，另外3例发生了逆转。两对分离株对阿米卡星的耐药性发生了变化。总之，确定了微生物学持续性感染的危险因素，抗分枝杆菌治疗期间MIC值的变化表明需要进行监测以便及时调整治疗方案。重要性非结核分枝杆菌肺病（NTM-PD）因其在全球范围内发病率不断上升、治愈率低和复发率高，已被公认为一个重要的公共卫生问题。NTM-PD对许多一线抗结核药物具有天然耐药性，这限制了治疗选择。据报道，[具体菌种名称]是最重要的致病NTM，在中国NTM-PD中占比最高。先前的一项研究表明，治疗6个月后微生物学反应不佳可预测治疗失败。本研究调查了肺部疾病患者治疗至第6个月时痰培养持续阳性相关的危险因素以及临床环境中最低抑菌浓度模式的变化。这些信息可能有助于识别治疗失败风险较高的患者，并及时提供必要的干预措施。
