达托霉素与标准疗法治疗金黄色葡萄球菌引起的菌血症和心内膜炎的比较。

Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus.

作者信息

Fowler Vance G, Boucher Helen W, Corey G Ralph, Abrutyn Elias, Karchmer Adolf W, Rupp Mark E, Levine Donald P, Chambers Henry F, Tally Francis P, Vigliani Gloria A, Cabell Christopher H, Link Arthur Stanley, DeMeyer Ignace, Filler Scott G, Zervos Marcus, Cook Paul, Parsonnet Jeffrey, Bernstein Jack M, Price Connie Savor, Forrest Graeme N, Fätkenheuer Gerd, Gareca Marcelo, Rehm Susan J, Brodt Hans Reinhardt, Tice Alan, Cosgrove Sara E

机构信息

Duke University Medical Center, Durham, NC 27710, USA.

出版信息

N Engl J Med. 2006 Aug 17;355(7):653-65. doi: 10.1056/NEJMoa053783.

DOI:10.1056/NEJMoa053783

PMID:16914701

Abstract

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. (ClinicalTrials.gov number, NCT00093067 [ClinicalTrials.gov].).

摘要

背景

金黄色葡萄球菌菌血症和心内膜炎需要替代治疗方法。

方法

我们将124例患有或未患有心内膜炎的金黄色葡萄球菌菌血症患者随机分组，其中124例患者接受每日每公斤体重6毫克达托霉素静脉注射治疗，122例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治疗。主要疗效终点是治疗结束后42天的治疗成功情况。

结果

在改良意向性分析中，治疗结束42天后，120例接受达托霉素治疗的患者中有53例治疗成功，而115例接受标准治疗的患者中有48例治疗成功（44.2%对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先设定标准。在患有复杂性菌血症、右侧心内膜炎和耐甲氧西林金黄色葡萄球菌的患者亚组中，成功率相似。达托霉素治疗的微生物学失败率高于标准治疗（分别为19例和11例，P=0.17）。在达托霉素组19例微生物学失败的患者中，有6例出现了对达托霉素敏感性降低的分离株；同样，在用万古霉素治疗的患者分离株中也发现了对万古霉素敏感性降低的情况。与达托霉素治疗相比，标准治疗导致因停药而治疗失败的不良事件发生率略高（分别为17例和8例，P=0.06）。接受达托霉素治疗的患者中有11.0%发生了具有临床意义的肾功能不全，接受标准治疗的患者中有26.3%发生了肾功能不全（P=0.004）。