Kullar Ravina, Casapao Anthony M, Davis Susan L, Levine Donald P, Zhao Jing J, Crank Christopher W, Segreti John, Sakoulas George, Cosgrove Sara E, Rybak Michael J
Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA.
J Antimicrob Chemother. 2013 Dec;68(12):2921-6. doi: 10.1093/jac/dkt294. Epub 2013 Aug 8.
Despite significant medical advances, infective endocarditis (IE) remains an infection associated with high morbidity and mortality. The objective was to assess the safety and efficacy of high-dose daptomycin, defined as ≥ 8 mg/kg/day, in patients with confirmed or suspected staphylococcal and/or enterococcal IE.
This was a multicentre, retrospective observational study (2005-11). Adult patients, not undergoing haemodialysis, with blood cultures positive for staphylococci or enterococci and a definitive or possible diagnosis of IE, who received daptomycin ≥ 8 mg/kg/day (based on total body weight) for ≥ 72 h were included.
Seventy patients met the inclusion criteria and comprised 33 (47.1%) with right-sided IE (RIE), 35 (50%) with left-sided IE (LIE) and 2 with both RIE and LIE. Several patients had concomitant sites of infection, with bone/joint infection being most prevalent (12.9%). Sixty-five patients received daptomycin as salvage therapy. Pathogens were isolated from 64 patients, with methicillin-resistant Staphylococcus aureus as the most common organism (84.4%), followed by vancomycin-resistant Enterococcus faecium (7.8%). The median (IQR) daptomycin dose was 9.8 mg/kg/day (8.2-10.0 mg/kg/day), and was similar in RIE and LIE patients (9.8 and 9.3 mg/kg/day, respectively). A total of 24 (34.3%) received combination therapy. For those patients with pathogens isolated (n = 64), the organism was eradicated in 57 (89.1%) patients. Among 64 clinically evaluable patients, 55 (85.9%) achieved clinical success. No patients required discontinuation of high-dose daptomycin due to creatine phosphokinase elevations.
Patients with both RIE and LIE had successful outcomes with high-dose daptomycin therapy. Additional clinical trials evaluating high daptomycin dosages in patients with IE are warranted.
尽管医学取得了重大进展，但感染性心内膜炎（IE）仍然是一种发病率和死亡率都很高的感染性疾病。本研究的目的是评估高剂量达托霉素（定义为≥8mg/kg/天）对确诊或疑似葡萄球菌和/或肠球菌性IE患者的安全性和有效性。
这是一项多中心回顾性观察研究（2005 - 2011年）。纳入未进行血液透析、血培养葡萄球菌或肠球菌阳性且确诊或可能诊断为IE、接受达托霉素≥8mg/kg/天（基于总体重）且疗程≥72小时的成年患者。
70例患者符合纳入标准，其中33例（47.1%）为右侧IE（RIE），35例（50%）为左侧IE（LIE），2例同时患有RIE和LIE。部分患者有合并感染部位，其中骨/关节感染最为常见（12.9%）。65例患者接受达托霉素作为挽救治疗。64例患者分离出病原体，耐甲氧西林金黄色葡萄球菌是最常见的病原体（84.4%），其次是耐万古霉素屎肠球菌（7.8%）。达托霉素剂量的中位数（IQR）为9.8mg/kg/天（8.2 - 10.0mg/kg/天），RIE和LIE患者相似（分别为9.8和9.3mg/kg/天）。共有24例（34.3%）接受联合治疗。对于分离出病原体的患者（n = 64），57例（89.1%）患者的病原体被清除。在64例可进行临床评估的患者中，55例（85.9%）取得临床成功。没有患者因肌酸磷酸激酶升高而需要停用高剂量达托霉素。
高剂量达托霉素治疗RIE和LIE患者均取得了成功的结果。有必要开展更多临床试验来评估高剂量达托霉素治疗IE患者的疗效。
