Rationale

Whether two-drug therapy (clarithromycin and ethambutol) for Mycobacterium avium complex (MAC) pulmonary disease contributes to the development of macrolide-resistant MAC is unclear.

Objective

To compare the incidence of macrolide-resistant MAC between patients treated with two-drug therapy (clarithromycin and ethambutol) and the standard three-drug therapy (clarithromycin, ethambutol, and rifampicin) for MAC pulmonary disease.

Methods

We retrospectively reviewed 147 patients with treatment-naive MAC pulmonary disease who had received two-drug therapy (n = 47) or three-drug therapy (n = 100) between 1997 and 2016 at National Hospital Organization, Tenryu Hospital, Hamamatsu, Japan. The risk of development of macrolide-resistant MAC was evaluated by calculating the cumulative incidence rate using Gray's test.

Results

The median follow-up period was 74.5 months. During the follow-up period, one of the 47 patients (2.1%) in the two-drug group developed macrolide-resistant MAC, compared to 12 of the 100 patients (12.0%) in the three-drug group. The cumulative incidence rate of macrolide-resistant MAC was lower in the two-drug group than in the three-drug group (0.0023; 95% confidence interval, 0.002 to 0.107 versus 0.200; 95% confidence interval, 0.100 to 0.324, p = 0.0593).

Conclusions

These results suggest that two-drug treatment with clarithromycin and ethambutol for MAC pulmonary disease does not lead to a higher incidence of resistance acquisition to clarithromycin than the standard three-drug treatment.

中文翻译：

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克拉霉素和乙胺丁醇联合治疗后，对大环内酯类耐药的鸟分枝杆菌复杂的肺部疾病。

基本原理

鸟分枝杆菌复合物（MAC）肺部疾病的两种药物疗法（克拉霉素和乙胺丁醇）是否有助于大环内酯类耐药性MAC的发展尚不清楚。

目的

为了比较接受两种药物治疗（克拉霉素和乙胺丁醇）和标准的三种药物治疗（克拉霉素，乙胺丁醇和利福平）的MAC肺疾病患者对大环内酯类药物耐药的MAC发生率。

方法

我们回顾性分析了1997年至2016年之间在日本滨松市天龙医院的国立医院组织接受过两种药物治疗（n = 47）或三种药物治疗（n = 100）的147例初治MAC肺疾病患者。通过使用Gray检验计算累积发生率，评估了抗大环内酯类MAC发生的风险。

结果

中位随访期为74.5个月。在随访期间，两药组47例患者中有1例（2.1％）发生了大环内酯耐药的MAC，而三药组100例患者中有12例（12.0％）发生了大环内酯耐药。两药组中大环内酯类药物耐药MAC的累积发生率低于三药组（0.0023; 95％置信区间，0.002至0.107对0.200; 95％置信区间，0.100至0.324，p  = 0.0593 ）。

结论

这些结果表明，与标准的三药治疗相比，使用克拉霉素和乙胺丁醇的两种药物治疗MAC肺部疾病不会导致对克拉霉素产生耐药性的发生率更高。