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鸟分枝杆菌复合群肺病中克拉霉素最低抑菌浓度与治疗反应的关系

Relationship Between Clarithromycin Minimum Inhibitory Concentrations and Treatment Responses in Mycobacterium avium Complex Pulmonary Disease.

作者信息

Kim Joong-Yub, Hwang Hyeontaek, Yim DaHae, Choi Yunhee, Kim Taek Soo, Whang Jake, Kwak Nakwon, Yim Jae-Joon

机构信息

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.

出版信息

Clin Infect Dis. 2025 Mar 17;80(3):637-643. doi: 10.1093/cid/ciae546.

Abstract

BACKGROUND

Mycobacterium avium complex pulmonary disease (MAC-PD) is a chronic lung condition with rapidly increasing prevalence worldwide. Macrolides like azithromycin and clarithromycin are the backbone of long-term antibiotic therapy for progressive MAC-PD. The impact of minimum inhibitory concentrations (MICs), especially within the susceptible range, for macrolides on treatment responses remains unclear.

METHODS

We analyzed adult patients who started treatment for MAC-PD between 1 March 2009 and 1 March 2022 at Seoul National University Hospital. Patients were categorized into 4 groups according to the clarithromycin MICs of their causative strains at treatment initiation. Logistic regression was employed to evaluate the impact of clarithromycin MICs on the likelihood of microbiological cure. Companion drugs and their MICs, alongside clinical characteristics like age, sex, body mass index, cavity presence, acid-fast bacilli smear positivity, causative species, and erythrocyte sedimentation rate were adjusted in multivariable analysis.

RESULTS

Four-hundred thirty-six patients (median age, 65 years; 34% men) were included. Microbiological cure rates were 51.8%, 51.9%, 50.0%, and 18.2% for patients with clarithromycin MICs ≤0.5, 1-2, 4-8, and ≥32 µg/mL, respectively (P = .181). No significant differences in microbiological cure rates were observed across varying levels of clarithromycin MICs within the susceptible range (≤8 µg/mL). Relative to patients with clarithromycin-susceptible strains, patients with MICs ≥32 µg/mL had an odds ratio of 0.25 for achieving microbiological cure (95% confidence interval [CI]: 0.06-1.07; P = .06).

CONCLUSIONS

Treatment responses were comparable among patients with strains having clarithromycin MICs within the susceptible range but were likely to be worse for patients with strains having MICs ≥32 µg/mL.

摘要

背景

鸟分枝杆菌复合群肺部疾病(MAC-PD)是一种慢性肺部疾病,在全球范围内患病率迅速上升。阿奇霉素和克拉霉素等大环内酯类药物是进展性MAC-PD长期抗生素治疗的基础。大环内酯类药物的最低抑菌浓度(MIC),尤其是在敏感范围内,对治疗反应的影响仍不清楚。

方法

我们分析了2009年3月1日至2022年3月1日在首尔国立大学医院开始接受MAC-PD治疗的成年患者。根据治疗开始时致病菌株的克拉霉素MIC,将患者分为4组。采用逻辑回归评估克拉霉素MIC对微生物学治愈可能性的影响。在多变量分析中对辅助药物及其MIC,以及年龄、性别、体重指数、空洞存在情况、抗酸杆菌涂片阳性、致病菌种和红细胞沉降率等临床特征进行了调整。

结果

纳入了436例患者(中位年龄65岁;34%为男性)。克拉霉素MIC≤0.5、1-2、4-8和≥32 μg/mL的患者微生物学治愈率分别为51.8%、51.9%、50.0%和18.2%(P = 0.181)。在敏感范围内(≤8 μg/mL),不同水平的克拉霉素MIC之间未观察到微生物学治愈率的显著差异。与克拉霉素敏感菌株的患者相比,MIC≥32 μg/mL的患者实现微生物学治愈的比值比为0.25(95%置信区间[CI]:0.06-1.07;P = 0.06)。

结论

克拉霉素MIC在敏感范围内的菌株患者的治疗反应相当,但MIC≥32 μg/mL的菌株患者的治疗反应可能更差。

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