Katz D E, Lindfield K C, Steenbergen J N, Benziger D P, Blackerby K J, Knapp A G, Martone W J
Cubist Pharmaceuticals, Inc., Lexington, MA 02421, USA.
Int J Clin Pract. 2008 Sep;62(9):1455-64. doi: 10.1111/j.1742-1241.2008.01854.x. Epub 2008 Jul 25.
Methicillin-susceptible and -resistant (MRSA) Staphylococcus aureus are significant causes of complicated skin and skin structure infections (cSSSI). The bactericidal antibiotic daptomycin is approved for gram-positive cSSSI at 4 mg/kg/day for 7-14 days, but the optimal dose level and duration of therapy have not been firmly established. This pilot study evaluated the efficacy and safety of daptomycin at 10 mg/kg every 24 h for 4 days [high-dose short duration (HDSD) regimen] vs. standard of care therapy with vancomycin or semi-synthetic penicillin for the treatment of cSSSI.
This was a semi-single blind, randomised, multicentre, comparative trial. The primary efficacy end-point was the clinical response 7-14 days posttherapy.
One hundred patients were randomised; 48 in each arm were treated. The treatment groups were well balanced with respect to demographics, comorbidities and the type of infection (75% because of MRSA). Overall, clinical success rates were 75.0% (36/48) for daptomycin and 87.5% (42/48) for comparator (95% confidence interval for the difference: -27.9, 2.9). The median duration of comparator therapy was 8 days. Two comparator patients and no daptomycin patients experienced treatment-related serious adverse events requiring hospitalisation.
We found that the HDSD regimen had a safety profile similar to that seen in previous studies. Although the differences were not statistically significant, clinical success rates for comparator were higher than for daptomycin. In post hoc analyses HDSD daptomycin performed better in some subgroups (e.g. outpatients) than in others (e.g. certain MRSA infections). These observations require confirmation in larger trials.
甲氧西林敏感和耐药金黄色葡萄球菌（MRSA）是复杂性皮肤和皮肤结构感染（cSSSI）的重要病因。杀菌性抗生素达托霉素已被批准用于治疗革兰氏阳性菌引起的cSSSI，剂量为4mg/kg/天，疗程7 - 14天，但最佳剂量水平和治疗持续时间尚未完全确定。本初步研究评估了每24小时给予达托霉素10mg/kg、共4天的高剂量短疗程（HDSD）方案与使用万古霉素或半合成青霉素的标准治疗方案治疗cSSSI的疗效和安全性。
这是一项半单盲、随机、多中心的对照试验。主要疗效终点是治疗后7 - 14天的临床反应。
100例患者被随机分组，每组48例接受治疗。治疗组在人口统计学、合并症和感染类型（75%由MRSA引起）方面均衡性良好。总体而言，达托霉素组的临床成功率为75.0%（36/48），对照治疗组为87.5%（42/48）（差异的95%置信区间：-27.9，2.9）。对照治疗组的中位疗程为8天。2例接受对照治疗的患者和0例接受达托霉素治疗的患者发生了需要住院治疗的与治疗相关的严重不良事件。
我们发现HDSD方案的安全性与既往研究相似。虽然差异无统计学意义，但对照治疗组的临床成功率高于达托霉素组。在事后分析中，HDSD方案的达托霉素在某些亚组（如门诊患者）中的表现优于其他亚组（如某些MRSA感染）。这些观察结果需要在更大规模的试验中得到证实。
