Department of Pharmacy, Yokohama General Hospital, Yokohama, Japan.
Division of Pharmacodynamics, Keio University Faculty of Pharmacy, Tokyo, Japan.
Br J Clin Pharmacol. 2023 Apr;89(4):1291-1303. doi: 10.1111/bcp.15671. Epub 2023 Feb 13.
Standard doses of daptomycin at 4 and 6 mg/kg were used for the treatment of skin and soft tissue for infections and bacteraemia, respectively. However, increased doses of daptomycin are recommended for complicated infections by Gram-positive organisms.
A systematic review was conducted using 4 databases. We compared treatment success between standard-dose (SD, 4-6 mg/kg) and high-dose (HD, >6 mg/kg) daptomycin in patients with all-cause bacteraemia, complicated bacteraemia, infective endocarditis, osteomyelitis and foreign body/prosthetic infection as the primary outcome. We also compared the success between SD and HD2 (≥8 mg/kg) daptomycin treatments in patients with these diseases as the secondary outcome. The incidence of creatine phosphokinase (CPK) elevation was evaluated as safety.
In patients with complicated bacteraemia and infective endocarditis, the treatment success was significantly lower in the SD group than in the HD group (odds ratio [OR] 0.48, 95% confidence interval [CI] 0.30-0.76 and OR 0.50, 95% CI 0.30-0.82) and HD2 group (OR 0.38, 95% CI 0.21-0.69 and OR 0.30, 95% CI 0.15-0.60), respectively. A significant difference was demonstrated only in the HD2 group in patients with bacteraemia, including simple infection. SD did not decrease the success rate for the treatment of osteomyelitis and foreign body/prosthetic infection. The incidence of elevated CPK was significantly lower in SD group than in HD group.
SD daptomycin was associated with significantly lower treatment success than HD in patients with complicated bacteraemia/infective endocarditis. The CPK elevation should be considered in patients treated with high daptomycin doses.
万古霉素的标准剂量为 4 和 6mg/kg，分别用于治疗皮肤和软组织感染和菌血症。然而，对于革兰氏阳性菌引起的复杂感染，建议使用更高剂量的万古霉素。
我们使用 4 个数据库进行了系统评价。我们将标准剂量（SD，4-6mg/kg）和高剂量（HD，>6mg/kg）万古霉素治疗所有病因菌血症、复杂菌血症、感染性心内膜炎、骨髓炎和异物/假体感染患者的治疗成功率作为主要结局进行比较。我们还将 SD 和 HD2（≥8mg/kg）万古霉素治疗这些疾病患者的成功率作为次要结局进行了比较。评估肌酸磷酸激酶（CPK）升高的发生率作为安全性。
在复杂菌血症和感染性心内膜炎患者中，SD 组的治疗成功率明显低于 HD 组（比值比[OR] 0.48，95%置信区间[CI] 0.30-0.76 和 OR 0.50，95%CI 0.30-0.82）和 HD2 组（OR 0.38，95%CI 0.21-0.69 和 OR 0.30，95%CI 0.15-0.60）。仅在包括单纯感染在内的菌血症患者中，HD2 组的差异具有统计学意义。SD 并未降低骨髓炎和异物/假体感染的治疗成功率。CPK 升高的发生率在 SD 组明显低于 HD 组。
与 HD 相比，SD 万古霉素治疗复杂菌血症/感染性心内膜炎患者的治疗成功率明显较低。在使用高剂量万古霉素治疗的患者中应考虑 CPK 升高的问题。
