达托霉素致横纹肌溶解症的文献病例分析

Literature analysis of rhabdomyolysis induced by daptomycin

目的 了解达托霉素致横纹肌溶解症的临床特点.方法 检索PubMed、Elsevier Science Direct、Embase、Springer-link、Wiley Online Library、CNKI、万方数据库（截至2017年1月）,收集期刊文献报道的达托霉素致横纹肌溶解症病例,提取相关数据进行描述性统计分析,并对符合入选标准的病例进行不良反应关联性评价. 结果 共收集到达托霉素致横纹肌溶解症患者10例,8例有性别、年龄记录,其中男性3例、女性5例,年龄34~70岁、平均54岁;10例既往均无肌肉疼痛或不适的病史.4例患者达托霉素实际用药剂量未超过说明书要求最大剂量（5~6 mg·kg-1·24 h-1）;6例实际用药剂量高于说明书要求（分别为7.2 mg·kg-1·48 h-1、8 mg·kg-1·24 h-1、6 mg·kg-1·12 h-1、10 mg·kg-1·24 h-1及6.5 mg·kg-1·24 h-1）;1例达托霉素用量记录为500 mg·24 h-1,因病历中未记录患者体重,无法评价用药剂量是否合理.10例患者出现横纹肌溶解症的时间为用药后2~16 d,平均8 d .临床主要表现为肌痛（8例）、肌无力（6例）、肌球蛋白尿（2例）等;血清CK 水平均异常升高,为1 754~25 234 U/L,平均（13 044±8 351）U/L. 9例患者有联用药物记录,其中联用1、2、3种药物者各2例,5种者1例,8种者2例;联用药物包括降脂药、抗生素、降糖药及抗病毒药物等.出现横纹肌溶解症后均停用达托霉素并给予对症治疗,4例患者5~18 d后血清CK水平恢复正常;5例3~14 d后血清CK水平有不同程度的恢复（由1 754~25 234 U/L降至125~7 647 U/L）;1例仅简单记录为血清CK恢复正常.3例患者在停药5~14 d症状缓解,7例患者未提及具体时间.9例患者的不良反应关联性评价为很可能,1例为可能;2例横纹肌溶解的发生可能与给药频率相关. 结论 达托霉素单用或与其他药物联用均可导致横纹肌溶解症,给药频率可能是其相关危险因素.停药并给予对症治疗,症状可缓解,血清CK水平可在2周左右恢复正常或明显下降.

Objective To understand the clinical characteristics of daptomycin induced rhabdomyolysis.Methods PubMed, Elsevier Science Direct, Embase, Springer-link, Wiley Online Library, CNKI, and Wanfang Data （to January 2017） were searched and case reports on daptomycin induced rhabdomyolysis were collected.Data related to rhabdomyolysis induced by daptomycin were analyzed descriptively.Relevance evaluation of case reports in accordance with inclusion criteria were performed.Results A total of 10 patients with rhabdomyolysis induced by daptomycin were collected.Of 10 patients, 8 cases′s gender were recorded, including 3 males and 5 females.Their ages were 34 to 70 years and the average age was 54 years.There were no muscle pain or discomfort history in all patients.Daptomycin dosage in 4 patients （5~6 mg·kg-1·24 h-1） did not exceed the maximum dosage recommended in instructions;daptomycin dosage in 6 patients （7.2 mg·kg-1·48 h-1, 8 mg·kg-1·24 h-1, 6 mg·kg-1·12 h-1, 10 mg·kg-1·24 h-1 and 6.5 mg·kg-1·24 h-1） were higher than that recommended in instructions;daptomycin dosage in 1 patient was 500 mg·24 h-1 （the dosage could not be evaluated because of no body weight record）.The time of rhabdomyolysis occurrence after daptomycin treatment was 2-16 days and the average time was 8 days.As the main clinical manifestations, 8 patients had myalgia, 6 patients had muscular weakness, and 2 patients had myoglobulinuria;serum CK levels were all abnormally elevated to 1 754-25 234 U/L with an average level of （13 044±8 351） U/L.Combination drugs in 9 patients were recorded;of them, the kinds of combination drugs were 1, 2, 3, 5, and 8 drugs in 2, 2, 2, 1, and 2 patients, respectively.The combination drugs included antilipemic, antibiotics, antidiabetic agents, antiviral drugs and etc.Daptomycin was stopped after rhabdomyolysis occurrence, symptomatic treatments were given;5-18 days later, serum CK levels normalized in 4 patients, and 3-14 days later, serum CK levels decreased to some degrees （from 1 754-25 234 U/L to 125-7 647 U/L） in 5 patients;serum CK level normalized in 1 patient and the time was not mentioned.Symptoms were improved 5-14 days after daptomycin withdrawal in 3 patients and the improvement time was not mentioned in 7 patients.Relevance evaluation of adverse reactions were probably in 9 patients and possible in 1 patient.The rhabdomyolysis occurrence was related to frequency of administration in 2 patients.Conclusions Daptomycin alone or combined with other drugs may cause rhabdomyolysis.The frequency of administration is likely to be a risk factor.Stopping daptomycin and giving symptomatic treatments could improve symptoms and the serum CK levels may return to normal or markedly decrease within about 2 weeks.