Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus
Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus
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DOI：
10.1056/nejmoa053783
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发表时间：
2006-08-17
影响因子：
158.5
通讯作者：
Cosgrove, Sara E.
中科院分区：
文献类型：
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作者：
Fowler, Vance G., Jr.;Boucher, Helen W.;Cosgrove, Sara E.
背景：金黄色葡萄球菌菌血症和心内膜炎需要替代疗法。方法：我们随机分配 124 名患有或不患有心内膜炎的金黄色葡萄球菌菌血症患者接受每天每公斤体重 6 毫克的达托霉素静脉注射，122 名患者接受初始低剂量庆大霉素加抗葡萄球菌青霉素或万古霉素。主要疗效终点是治疗结束后 42 天的治疗成功。 结果：在改良的意向治疗分析中，治疗结束后 42 天，接受达托霉素治疗的 120 名患者中有 53 名获得成功，而接受标准治疗的 115 名患者中有 48 名获得成功（分别为 44.2% 和 41.7%；绝对差异为 2.4%；95% 置信区间为 -10.2 至15.1%）。我们的结果符合达托霉素非劣效性的预定标准。患有复杂性菌血症、右侧心内膜炎和耐甲氧西林金黄色葡萄球菌的患者亚组的成功率相似。与标准治疗相比，达托霉素治疗的微生物学失败率较高（19 例患者与 11 例患者，P=0.17）。达托霉素组 19 名微生物学失败的患者中，有 6 名出现了对达托霉素敏感性降低的分离株；同样，在接受万古霉素治疗的患者中分离出的菌株对万古霉素的敏感性降低。与达托霉素治疗相比，标准治疗的不良事件发生率较高，但由于停止治疗而导致治疗失败（17 例 vs. 8 例，P=0.06）。接受达托霉素治疗的患者中有 11.0% 出现临床显着的肾功能不全，而接受标准治疗的患者则有 26.3% 出现临床显着的肾功能障碍 (P=0.004)。 结论：达托霉素（每天 6 毫克/公斤）对于金黄色葡萄球菌菌血症和右侧心内膜炎的治疗效果并不逊于标准治疗。
BACKGROUND:Alternative therapies for Staphylococcus aureus bacteremia and endocarditis are needed.METHODS:We randomly assigned 124 patients with S. aureus bacteremia with or without endocarditis to receive 6 mg of daptomycin intravenously per kilogram of body weight daily and 122 to receive initial low-dose gentamicin plus either an antistaphylococcal penicillin or vancomycin. The primary efficacy end point was treatment success 42 days after the end of therapy.RESULTS:Forty-two days after the end of therapy in the modified intention-to-treat analysis, a successful outcome was documented for 53 of 120 patients who received daptomycin as compared with 48 of 115 patients who received standard therapy (44.2 percent vs. 41.7 percent; absolute difference, 2.4 percent; 95 percent confidence interval, -10.2 to 15.1 percent). Our results met prespecified criteria for the noninferiority of daptomycin. The success rates were similar in subgroups of patients with complicated bacteremia, right-sided endocarditis, and methicillin-resistant S. aureus. Daptomycin therapy was associated with a higher rate of microbiologic failure than was standard therapy (19 vs. 11 patients, P=0.17). In 6 of the 19 patients with microbiologic failure in the daptomycin group, isolates with reduced susceptibility to daptomycin emerged; similarly, a reduced susceptibility to vancomycin was noted in isolates from patients treated with vancomycin. As compared with daptomycin therapy, standard therapy was associated with a nonsignificantly higher rate of adverse events that led to treatment failure due to the discontinuation of therapy (17 vs. 8, P=0.06). Clinically significant renal dysfunction occurred in 11.0 percent of patients who received daptomycin and in 26.3 percent of patients who received standard therapy (P=0.004).CONCLUSIONS:Daptomycin (6 mg per kilogram daily) is not inferior to standard therapy for S. aureus bacteremia and right-sided endocarditis.