达托霉素相关急性嗜酸性粒细胞性肺炎

Daptomycin associated acute eosinophilic pneumonia

目的：了解达托霉素引起急性嗜酸性粒细胞性肺炎（AEP）的临床特征、发生原因及治疗措施。方法：检索Pub Med数据库,收集2005年–2015年5月国外医学文献中达托霉素所致AEP的文献,对患者的一般情况、用药情况、给药剂量、AEP临床表现及影像学表现、发生时间和特点、治疗与转归等进行分析。结果：共纳入13篇文献,合计27例患者。其中,男性23例和女性4例,平均年龄64岁,大部分用药剂量范围为4.4-8.0 mg·kg^-1·d^-1,发生时间中位数为开始给药后14 d,症状改善时间中位数为2 d。发热、呼吸困难是达托霉素引起AEP的主要临床症状。66.67%患者肺泡灌洗液嗜酸性粒细胞比例增多,肺部影像学多提示为肺泡腔内实变浸润影和磨玻璃样影,停药和对症治疗后,症状很快消除,17例患者痊愈,10例好转。结论：达托霉素少见诱发AEP,与用药剂量可能无相关性,AEP的病理生理机制涉及免疫反应,通过各种机制使嗜酸性粒细胞迁移到肺泡,因此通常需要至少一周的时间才出现肺部并发症。停药并使用糖皮质激素、氧疗等对症治疗后,预后良好。建议临床医生在使用达托霉素治疗过程中,早期识别AEP这种疾病是至关重要的。

Objective： To investigate the clinical features, causes and therapeutic measures of daptomycin associated acute eosinophilic pneumonia（AEP）. Methods： Literature about AEP induced by daptomycin published in foreign language from 2005 to May 2015 was collected by retrieving Pub Med database. The baseline characteristics of patients, the dosage and administration of daptomycin, the clinical manifestations and imaging performance, onset time, the outcome of treatment and prognosis of the AEP were analyzed. Results： There were totally 27 patients（23 men and 4 women） suffered from daptomycin associated AEP in 13 case reports. The average age was 64. Most administration dose ranged from 4.4 to 8.0 mg·kg^-1·d^-1 The median onset time of daptomycin associated AEP was 14 days after administration and the median time of recovery was 2 days. Fever and dyspnoea were the main clinical symptoms of AEP induced by daptomycin. About 66.67% of patients had higher number of eosinophilic granulocyte in alveolar lavage fluid eosinophils. Most CT scan of the patients showed bilateral infiltrates and ground glass consolidation. After withdrawal and symptomatic treatment, the symptoms eliminated quickly. Among 27 patients, 17 patients were cured and 10 patients were getting better. Conclusion： Daptomycin can rarely cause AEP. The dosage seems to have nothing to do with daptomycin associated AEP. The physiopathologic mechanism of AEP is considered to be involved in the immunological reactions. Eosinophils migrated to alveoli through various mechanisms. So the symptom usually comes out within more than 1 week after administration. If AEP is considered to be caused by daptomycin, prompt withdrawal is necessary. The management of AEP induced by daptomycin includes administration of oxygen, glucocorticoid, mechanical ventilation and other symptomatic treatments. It is very important to be aware of daptomycin associated AEP as early as possible during the therapeutic process.